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1.
Pharmacol Rev ; 62(4): 588-631, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21079038

RESUMEN

There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB(1), non-CB(2) established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB(1) and/or CB(2) receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel "CB(3)" cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB(1), non-CB(2) pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB(3) receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB(1) receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB(1)/CB(2) receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB(1), non-CB(2) cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.


Asunto(s)
Receptores de Cannabinoides/metabolismo , Agonistas de Receptores de Cannabinoides , Antagonistas de Receptores de Cannabinoides , Moduladores de Receptores de Cannabinoides/metabolismo , Cannabinoides/metabolismo , Humanos , Ligandos , Filogenia , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/antagonistas & inhibidores , Receptor Cannabinoide CB2/metabolismo , Terminología como Asunto
2.
Brain Struct Funct ; 225(1): 249-284, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31807925

RESUMEN

Cholecystokinin (CCK) is a neuropeptide that modulates processes such as digestion, satiety, and anxiety. CCK-type peptides have been characterized in jawed vertebrates and invertebrates, but little is known about CCK-type signalling in the most ancient group of vertebrates, the agnathans. Here, we have cloned and sequenced a cDNA encoding a sea lamprey (Petromyzon marinus L.) CCK-type precursor (PmCCK), which contains a CCK-type octapeptide sequence (PmCCK-8) that is highly similar to gnathostome CCKs. Using mRNA in situ hybridization, the distribution of PmCCK-expressing neurons was mapped in the CNS of P. marinus. This revealed PmCCK-expressing neurons in the hypothalamus, posterior tubercle, prethalamus, nucleus of the medial longitudinal fasciculus, midbrain tegmentum, isthmus, rhombencephalic reticular formation, and the putative nucleus of the solitary tract. Some PmCCK-expressing neuronal populations were only observed in adults, revealing important differences with larvae. We generated an antiserum to PmCCK-8 to enable immunohistochemical analysis of CCK expression, which revealed that GABA or glutamate, but not serotonin, tyrosine hydroxylase or neuropeptide Y, is co-expressed in some PmCCK-8-immunoreactive (ir) neurons. Importantly, this is the first demonstration of co-localization of GABA and CCK in neurons of a non-mammalian vertebrate. We also characterized extensive cholecystokinergic fibre systems of the CNS, including innervation of habenular subnuclei. A conspicuous PmCCK-8-ir tract ascending in the lateral rhombencephalon selectively innervates a glutamatergic population in the dorsal isthmic grey. Interestingly, this tract is reminiscent of the secondary gustatory/visceral tract of teleosts. In conclusion, this study provides important new information on the evolution of the cholecystokinergic system in vertebrates.


Asunto(s)
Encéfalo/citología , Encéfalo/metabolismo , Colecistoquinina/metabolismo , Neuronas/citología , Neuronas/metabolismo , Petromyzon/anatomía & histología , Petromyzon/metabolismo , Precursores de Proteínas/metabolismo , Animales , Evolución Biológica , ADN Complementario/metabolismo , Hibridación in Situ , ARN Mensajero/metabolismo , Maduración Sexual , Transducción de Señal , Ácido gamma-Aminobutírico/metabolismo
3.
Handb Exp Pharmacol ; (168): 283-97, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16596778

RESUMEN

The endocannabinoid signalling system in mammals comprises several molecular components, including cannabinoid receptors (e.g. CB1, CB2), putative endogenous ligands for these receptors [e.g. anandamide, 2-arachidonoylglycerol (2-AG)] and enzymes involved in the biosynthesis and inactivation of anandamide (e.g. NAPE-PLD, FAAH) and 2-AG (e.g. DAG lipase, MGL). In this review we examine the occurrence of these molecules in non-mammalian organisms (in particular, animals and plants) by surveying published data and by basic local alignment search tool (BLAST) analysis of the GenBank database and of genomic sequence data from several vertebrate and invertebrate species. We conclude that the ability of cells to synthesise molecules that are categorised as "endocannabinoids" in mammals is an evolutionarily ancient phenomenon that may date back to the unicellular common ancestor of animals and plants. However, exploitation of these molecules for intercellular signalling may have occurred independently in different lineages during the evolution of the eukaryotes. The CB1- and CB2-type receptors that mediate effects of endocannabinoids in mammals occur throughout the vertebrates, and an orthologue of vertebrate cannabinoid receptors was recently identified in the deuterostomian invertebrate Ciona intestinalis (CiCBR). However, orthologues of the vertebrate cannabinoid receptors are not found in protostomian invertebrates (e.g. Drosophila, Caenorhabditis elegans). Therefore, it is likely that a CB1/CB2-type cannabinoid receptor originated in a deuterostomian invertebrate. This phylogenetic information provides a basis for exploitation of selected non-mammalian organisms as model systems for research on endocannabinoid signalling.


Asunto(s)
Moduladores de Receptores de Cannabinoides/fisiología , Endocannabinoides , Transducción de Señal/fisiología , Amidohidrolasas/análisis , Animales , Ácidos Araquidónicos/análisis , Ácidos Araquidónicos/biosíntesis , Evolución Biológica , Glicéridos/análisis , Glicéridos/biosíntesis , Humanos , Filogenia , Alcamidas Poliinsaturadas , Receptor Cannabinoide CB1/análisis , Receptor Cannabinoide CB2/análisis
4.
Mar Genomics ; 24 Pt 2: 177-83, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26472700

RESUMEN

Opsins--G-protein coupled receptors involved in photoreception--have been extensively studied in the animal kingdom. The present work provides new insights into opsin-based photoreception and photoreceptor cell evolution with a first analysis of opsin sequence data for a major deuterostome clade, the Ambulacraria. Systematic data analysis, including for the first time hemichordate opsin sequences and an expanded echinoderm dataset, led to a robust opsin phylogeny for this cornerstone superphylum. Multiple genomic and transcriptomic resources were surveyed to cover each class of Hemichordata and Echinodermata. In total, 119 ambulacrarian opsin sequences were found, 22 new sequences in hemichordates and 97 in echinoderms (including 67 new sequences). We framed the ambulacrarian opsin repertoire within eumetazoan diversity by including selected reference opsins from non-ambulacrarians. Our findings corroborate the presence of all major ancestral bilaterian opsin groups in Ambulacraria. Furthermore, we identified two opsin groups specific to echinoderms. In conclusion, a molecular phylogenetic framework for investigating light-perception and photobiological behaviors in marine deuterostomes has been obtained.


Asunto(s)
Cordados no Vertebrados/genética , Equinodermos/genética , Evolución Molecular , Opsinas/metabolismo , Filogenia , Secuencia de Aminoácidos , Animales , Regulación de la Expresión Génica , Modelos Moleculares , Datos de Secuencia Molecular , Opsinas/genética , Conformación Proteica
5.
J Comp Neurol ; 422(2): 159-71, 2000 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-10842224

RESUMEN

The CB(1)-type cannabinoid receptor mediates physiologic effects of Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of the drug marijuana. In this report, the authors analyse the expression of CB(1) in the rat brain by using antibodies to the C-terminal 13 amino acids of the receptor. Western blot analysis of rat brain membranes revealed a prominent immunoreactive band with a molecular mass ( approximately 53 kDa) consistent with that predicted for CB(1) from the rat cDNA sequence. In addition, however, less intense immunoreactive bands corresponding to glycosylated ( approximately 62 kDa) and putative N-terminally shorter ( approximately 45 kDa) isoforms of CB(1) were detected. The distribution of CB(1)-immunoreactivity in rat brain was similar to the distribution of binding sites for radiolabelled cannabinoids, with high levels of expression in the olfactory system, the hippocampal formation, the basal ganglia, the cerebellum, and the neocortex. This provides important evidence that CB(1) is likely to be largely responsible for mediating effects of cannabinoids in the brain. CB(1) immunoreactivity was associated with nerve fibre systems and axon terminals but was not detected in neuronal somata. This is consistent with the presynaptic inhibitory effects of cannabinoids on neurotransmitter release in the brain. Detailed immunocytochemical analysis of anatomically or functionally related regions of the brain revealed the location of CB(1) receptors within identified neural circuits. Determination of the cellular and subcellular location of CB(1) within known neuronal circuits of the brain provides an anatomic framework for interpretation of the neurophysiologic and behavioural effects of cannabinoids.


Asunto(s)
Encéfalo/citología , Encéfalo/metabolismo , Receptores de Droga/metabolismo , Animales , Ganglios Basales/citología , Ganglios Basales/metabolismo , Western Blotting , Mapeo Encefálico , Cerebelo/citología , Cerebelo/metabolismo , Hipocampo/citología , Hipocampo/metabolismo , Inmunohistoquímica , Neocórtex/citología , Neocórtex/metabolismo , Neuronas/citología , Neuronas/metabolismo , Bulbo Olfatorio/citología , Bulbo Olfatorio/metabolismo , Estructura Terciaria de Proteína , Ratas , Ratas Wistar , Receptores de Cannabinoides
6.
J Comp Neurol ; 422(4): 521-32, 2000 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-10861524

RESUMEN

In the adult locust, nitric oxide (NO) synthase is expressed in interneurons that innervate mechanosensory neuropils, indicating that NO may participate in mechanosensory processing. Here, we have identified potential neuronal targets of NO by localizing the expression and activity of soluble guanylyl cyclase (SGC), its principal molecular target in the nervous system. We used two complementary approaches, namely immunolocalization of SGC alpha-subunit (SGCalpha), and of cyclic GMP (cGMP) after exposure to an NO donor. The cell bodies, axons and central projections of thoracic exteroceptors, proprioceptors, auditory receptors, and chemoreceptors were strongly immunoreactive for SGCalpha. Strong SGCalpha immunoreactivity also occurred in all thoracic motor neurons, including their axon terminals. NO-donors induced a pattern of cGMP immunostaining that was similar to the distribution of SGCalpha, indicating that both sensory and motor neurons contain functional SGC. Therefore, NO may modulate both the input from these sensory neurons and the output of motor neurons. Although the expression of SGCalpha was highly consistent, NO donors did not always induce cGMP-staining in SGC-containing neurons, suggesting that SGC is coregulated by factors other than NO. Complementing previous reports in the visual and olfactory system, our results indicate a general role for NO-cGMP signaling in early sensory processing; diffusible signals may mediate a cross-adaptation or -sensitization within neural maps where similarly tuned neurons have adjacent projections, an anatomical arrangement shared by many sensory systems.


Asunto(s)
Vías Aferentes/química , Guanilato Ciclasa/análisis , Neuronas Motoras/química , Neuronas Aferentes/química , Óxido Nítrico/fisiología , Vías Aferentes/enzimología , Animales , GMP Cíclico/análisis , Femenino , Saltamontes/química , Saltamontes/enzimología , Neuronas Motoras/enzimología , Neuronas Aferentes/enzimología
7.
Neuroscience ; 119(2): 481-96, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12770562

RESUMEN

Fatty acid amide hydrolase (FAAH) catalyses hydrolysis of the endocannabinoid arachidonoylethanolamide ("anandamide") in vitro and regulates anandamide levels in the brain. In the cerebellar cortex, hippocampus and neocortex of the rat brain, FAAH is located in the somata and dendrites of neurons that are postsynaptic to axon fibers expressing the CB(1) cannabinoid receptor [Proc R Soc Lond B 265 (1998) 2081]. This complementary pattern of FAAH and CB(1) expression provided the basis for a hypothesis that endocannabinoids may function as retrograde signaling molecules at synapses in the brain [Proc R Soc Lond B 265 (1998) 2081; Phil Trans R Soc Lond 356 (2001) 381] and subsequent experimental studies have confirmed this [Science 296 (2002) 678]. To assess more widely the functions of FAAH in the brain and the potential impact of FAAH activity on the spatiotemporal dynamics of endocannabinoid signaling in different regions of the brain, here we have employed immunocytochemistry to compare the distribution of FAAH and CB(1) throughout the mouse brain, using FAAH(-/-) mice as negative controls to validate the specificity of FAAH-immunoreactivity observed in wild type animals. In many regions of the brain, a complementary pattern of FAAH and CB(1) expression was observed, with FAAH-immunoreactive neuronal somata and dendrites surrounded by CB(1)-immunoreactive fibers. In these regions of the brain, FAAH may regulate postsynaptic formation of anandamide, thereby influencing the spatiotemporal dynamics of retrograde endocannabinoid signaling. However, in some regions of the brain such as the globus pallidus and substantia nigra pars reticulata, CB(1) receptors are abundant but with little or no associated FAAH expression and in these brain regions the spatial impact and/or duration of endocannabinoid signaling may be less restricted than in regions enriched with FAAH. A more complex situation arises in several regions of the brain where both FAAH and CB(1) are expressed but in a non-complementary pattern, with FAAH located in neurons and/or oligodendrocytes that are proximal but not postsynaptic to CB(1)-expressing axon fibers. Here FAAH may nevertheless influence endocannabinoid signaling but more remotely. Finally, there are regions of the brain where FAAH-immunoreactive neurons and/or oligodendrocytes occur in the absence of CB(1)-immunoreactive fibers and here FAAH may be involved in regulation of signaling mediated by other endocannabinoid receptors or by receptors for other fatty acid amide signaling molecules. In conclusion, by comparing the distribution of FAAH and CB(1) in the mouse brain, we have provided a neuroanatomical framework for comparative analysis of the role of FAAH in regulation of the spatiotemporal dynamics of retrograde endocannabinoid signaling in different regions of the brain.


Asunto(s)
Amidohidrolasas/análisis , Encéfalo/metabolismo , Receptores de Droga/análisis , Amidohidrolasas/fisiología , Animales , Encéfalo/citología , Encéfalo/enzimología , Moduladores de Receptores de Cannabinoides , Endocannabinoides , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Receptores de Cannabinoides
8.
Neuroscience ; 119(3): 803-12, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12809701

RESUMEN

In this study we used in situ hybridisation and double-labelling immunohistochemistry to characterise cannabinoid receptor 1 (CB(1)) expression in rat lumbar dorsal root ganglion (DRG) neurons.Approximately 25% of DRG neurons expressed CB(1) mRNA and displayed immunoreactivity for CB(1). Sixty-nine percent to 82% of CB(1)-expressing cells were also immunoreactive for neurofilament 200, indicative of myelinated A-fibre neurons, which tend to be large- and medium-sized DRG neurons (>600 microm(2)). Approximately 10% of CB1-expressing cells also expressed transient receptor potential vanilloid family ion channel 2 (TRPV2), the noxious heat-transducing channel found in medium to large lightly myelinated Adelta-fibre DRG neurons. Seventeen percent to 26% of CB(1)-expressing cells co-stained using Isolectin B4, 9-10% for calcitonin gene-related peptide and 11-20% for transient receptor potential vanilloid family ion channel 1 (TRPV1), predominantly markers of small non-myelinated C-fibre DRG neurons (<600 microm(2)). These findings suggest that whilst a wide range of DRG neuron phenotypes express CB(1), it is predominantly associated with myelinated fibres.


Asunto(s)
Ganglios Espinales/metabolismo , Glicoproteínas , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Amielínicas/metabolismo , Neuronas Aferentes/metabolismo , Nociceptores/metabolismo , Dolor/metabolismo , Receptores de Droga/genética , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Tamaño de la Célula/fisiología , Técnica del Anticuerpo Fluorescente , Ganglios Espinales/citología , Lectinas/metabolismo , Masculino , Mecanorreceptores/citología , Mecanorreceptores/metabolismo , Ratones , Ratones Noqueados , Fibras Nerviosas Mielínicas/ultraestructura , Fibras Nerviosas Amielínicas/ultraestructura , Proteínas de Neurofilamentos/metabolismo , Neuronas Aferentes/citología , Nociceptores/citología , Dolor/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Cannabinoides , Receptores de Droga/metabolismo
9.
Proc Biol Sci ; 261(1360): 139-45, 1995 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-7644545

RESUMEN

The recent isolation and characterization of the SALMFamide neuropeptides (S1 and S2) from the starfish Asterias rubens has initiated a series of single- and double-labelling immunocytochemical studies to ascertain their tissue distribution and cellular localization. Specific novel monoclonal and polyclonal antisera have been raised against these neuropeptides and used in optical immunocytochemistry (ICC). The results of the present study reveal, for the first time, the widespread neuronal distribution of S2 localized to axons and perikarya of the radial nerve cord and tube foot ectoneural nerve plexus. Double labelling revealed a predominantly separate localization for S1 and S2 immunoreactivity. The potential functional roles of S1 and S2 in the radial nerve cord (RNC) and tube feet of Asterias rubens are discussed.


Asunto(s)
Neuropéptidos/análisis , Estrellas de Mar/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales , Inmunohistoquímica , Locomoción , Datos de Secuencia Molecular , Sistema Nervioso/metabolismo
10.
Proc Biol Sci ; 265(1410): 2081-5, 1998 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-9842734

RESUMEN

CB1-type cannabinoid receptors in the brain mediate effects of the drug cannabis. Anandamide and sn-2 arachidonylglycerol (2-AG) are putative endogenous ligands for CB1 receptors, but it is not known which cells in the brain produce these molecules. Recently, an enzyme which catalyses hydrolysis of anandamide and 2-AG, known as fatty acid amide hydrolase (FAAH), was identified in mammals. Here we have analysed the distribution of FAAH in rat brain and compared its cellular localization with CB1-type cannabinoid receptors using immunocytochemistry. High concentrations of FAAH activity were detected in the cerebellum, hippocampus and neocortex, regions of the rat brain which are enriched with cannabinoid receptors. Immunocytochemical analysis of these brain regions revealed a complementary pattern of FAAH and CB1 expression with CB1 immunoreactivity occurring in fibres surrounding FAAH-immunoreactive cell bodies and/or dendrites. In the cerebellum, FAAH was expressed in the cell bodies of Purkinje cells and CB1 was expressed in the axons of granule cells and basket cells, neurons which are presynaptic to Purkinje cells. The close correspondence in the distribution of FAAH and CB1 in rat brain and the complementary pattern of FAAH and CB1 expression at the cellular level provides important new evidence that FAAH may participate in cannabinoid signalling mechanisms of the brain.


Asunto(s)
Amidohidrolasas/metabolismo , Encéfalo/metabolismo , Cannabinoides/metabolismo , Receptores de Droga/metabolismo , Transducción de Señal , Secuencia de Aminoácidos , Animales , Western Blotting , Encéfalo/enzimología , Inmunohistoquímica , Masculino , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley , Receptores de Cannabinoides
11.
Proc Biol Sci ; 243(1307): 121-7, 1991 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-1676515

RESUMEN

We have isolated two novel related neuropeptides from the radial nerve cords of the starfishes Asterias rubens and Asterias forbesi. One is an octapeptide with the amino acid sequence Gly-Phe-Asn-Ser-Ala-Leu-Met-Phe-NH2 and the other is a dodecapeptide with the amino acid sequence Ser-Gly-Pro-Tyr-Ser-Phe-Asn-Ser-Gly-Leu-Thr-Phe-NH2. The peptides were purified using high performance liquid chromatography (HPLC) and a radioimmunoassay for the molluscan FMRFamide-related neuropeptide, pQDPFLRFamide. Both peptides share minimal sequence identity with members of the family of FMRFamide-like peptides so we have designated them as founder members of a new family, the SALMFamides. We refer to the octapeptide as SALMFamide 1 (S1) and the dodecapeptide as SALMFamide 2 (S2). S1 and S2 are the first neuropeptides identified in species belonging to the phylum Echinodermata.


Asunto(s)
Sistema Nervioso/química , Neuropéptidos/aislamiento & purificación , Estrellas de Mar/fisiología , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Datos de Secuencia Molecular , Neuropéptidos/química , Radioinmunoensayo , Espectrometría de Masa Bombardeada por Átomos Veloces
12.
Peptides ; 12(3): 455-9, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1923925

RESUMEN

We have raised antisera in rabbits to a conjugate of thyroglobulin and Lys-Tyr-Ser-Ala-Leu-Met-Phe-NH2 (KYSALMFamide), a synthetic analog of the starfish neuropeptide S1 (Gly-Phe-Asn-Ser-Ala-Leu-Met- Phe-NH2). The sensitivity and specificity of two antisera (BL and SL) for S1 were established by testing the ability of S1 and structurally related peptides (SALMFamide-2 and various FMRFamide-related peptides) to displace iodinated KYSALMFamide from the serum antibodies in an RIA. Both antisera are sensitive to femtomolar amounts of S1. BL is highly specific for S1 but SL is not, since it is also able to detect femtomolar amounts of the FMRFamide-related peptides. We have used the BL antiserum in the RIA to monitor the purification of S1 immunoreactivity from radial nerve cord extracts of both Asterias rubens and Pycnopodia helianthoides. The partial amino acid sequence GFNSALM was obtained from automated Edman degradation sequencing of pure immunoreactive peaks from both species.


Asunto(s)
Neuropéptidos/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , FMRFamida , Inmunoquímica , Datos de Secuencia Molecular , Sistema Nervioso/química , Neuropéptidos/química , Neuropéptidos/inmunología , Estrellas de Mar
13.
Brain Res ; 780(1): 170-3, 1998 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-9497095

RESUMEN

Analysis of a G-protein coupled receptor fragment isolated from the leech CNS reveals that it is a chimeric cannabinoid/melanocortin receptor. Two regions of the leech sequence display high levels of amino acid identity with mammalian cannabinoid receptors while a third region is 98% identical to part of the bovine adrenocorticotropic hormone receptor. The leech receptor may therefore resemble the putative ancestor of mammalian cannabinoid and melanocortin receptors.


Asunto(s)
Cannabinoides/metabolismo , Proteínas de Unión al GTP/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Corticotropina/metabolismo , Receptores de Droga/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Secuencia de Aminoácidos , Animales , Bovinos , Humanos , Sanguijuelas , Datos de Secuencia Molecular , Receptores de Cannabinoides , Receptores de Melanocortina , Homología de Secuencia de Aminoácido
14.
Brain Res ; 800(1): 174-9, 1998 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-9685632

RESUMEN

The distribution of soluble guanylyl cyclase in the brain of the locust Schistocerca gregaria was analysed using antisera to a highly conserved region (X-peptide) of the Drosophila soluble guanylyl cyclase alpha-subunit (SGCalpha). Analysis of locust brain and locust eye homogenates in Western blots using X-peptide antisera revealed specific staining of a approximately 65 kDa band, which is similar to the expected molecular mass for a SGCalpha-subunit. SGCalpha-immunoreactivity was localized in identified neuronal components of several sensory systems including photoreceptors of the compound eyes and ocelli, large ocellar interneurons, antennal mechanosensory neurons and olfactory interneurons. These neurons are putative targets for the gas nitric oxide which activates guanylyl cyclase activity in the locust brain.


Asunto(s)
Guanilato Ciclasa/análisis , Guanilato Ciclasa/química , Neuronas/enzimología , Secuencia de Aminoácidos , Animales , Encéfalo/citología , Encéfalo/enzimología , Bovinos , Drosophila melanogaster/enzimología , Saltamontes/enzimología , Humanos , Inmunohistoquímica , Sustancias Macromoleculares , Datos de Secuencia Molecular , Peso Molecular , Células Fotorreceptoras de Invertebrados/citología , Células Fotorreceptoras de Invertebrados/enzimología , Ratas , Alineación de Secuencia , Homología de Secuencia de Aminoácido
15.
Brain Res ; 619(1-2): 344-6, 1993 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-7690676

RESUMEN

Nitric oxide (NO) is synthesized in mammalian neurons by Ca2+/calmodulin activated NO synthase and functions as a signalling molecule by activating soluble guanylyl cyclases in target cells. We demonstrate here that both NO synthase and NO-activated guanylyl cyclase are present in the brain of the locust Schistocerca gregaria. Our observations indicate, for the first time, that the NO-cyclic GMP signalling pathway exists in invertebrate nervous systems.


Asunto(s)
Aminoácido Oxidorreductasas/metabolismo , Encéfalo/metabolismo , Saltamontes/metabolismo , Óxido Nítrico/metabolismo , Animales , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Cinética , Neuronas/metabolismo , Óxido Nítrico Sintasa , Transducción de Señal
16.
Neurosci Lett ; 282(1-2): 13-6, 2000 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-10713385

RESUMEN

The enzyme fatty acid amide hydrolase (FAAH) catalyses hydrolysis of oleamide, a sleep-inducing lipid whose concentration in the cerebrospinal fluid (CSF) is elevated in sleep-deprived mammals. Previous studies have reported expression of FAAH by distinct populations of neurons in the rat brain. Here we demonstrate using immunocytochemical methods that FAAH is also expressed by non-neuronal epithelial cells of the rat choroid plexus. The choroid plexus is formed by invaginations of the pia mater into the ventricle cavities of the brain and an important function of the choroidal epithelium is to regulate production and composition of CSF. Therefore, the role of FAAH in epithelial cells of the choroid plexus may be to control the concentration of oleamide in the CSF and as such FAAH may exert an important regulatory role in shaping the duration and magnitude of the sleep-inducing effect of endogenously or exogenously derived oleamide.


Asunto(s)
Amidohidrolasas/metabolismo , Plexo Coroideo/metabolismo , Animales , Plexo Coroideo/citología , Células Epiteliales/metabolismo , Inmunohistoquímica , Ácidos Oléicos/líquido cefalorraquídeo , Ácidos Oléicos/fisiología , Ratas , Ratas Wistar , Sueño/fisiología
18.
Dev Biol ; 300(1): 434-60, 2006 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-16965768

RESUMEN

The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins.


Asunto(s)
Genoma , Proteínas del Tejido Nervioso/genética , Sistema Nervioso/crecimiento & desarrollo , Erizos de Mar/crecimiento & desarrollo , Animales , Axones/fisiología , Conexinas/genética , Electrofisiología , Humanos , Larva/fisiología , Mamíferos , Neuronas/fisiología , Filogenia , Erizos de Mar/clasificación , Erizos de Mar/genética , Sinapsis/fisiología , Factores de Transcripción/genética
19.
Biol Bull ; 194(3): 260-266, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28570203

RESUMEN

In vertebrates, nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS) and regulates relaxation of smooth muscle by activating the cyclic-GMP (cGMP) generating enzyme soluble guanylyl cyclase (SGC). Here we show that the NO-cGMP pathway mediates relaxation of the cardiac stomach in the starfish Asterias rubens. The NO-donors hydroxylamine, S-nitrosoglutathione (SNOG) and S-nitroso-N-acetylpenicillamine (SNAP) and the NOS substrate L-arginine cause relaxation of the cardiac stomach. The relaxing effect of SNAP is blocked by the SGC inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the relaxing effect of L-arginine is inhibited by ODQ and the NOS inhibitor Nw-monomethyl-L-arginine (L-NMMA). ODQ and methylene blue also cause contraction, which may be due to inhibition of the relaxing action of NO produced by cells in the cardiac stomach. These results suggest that NO is synthesized in the cardiac stomach and regulates relaxation by activating SGC. NO-cGMP-mediated relaxation of the cardiac stomach may be important during feeding in starfish where the relaxed stomach is everted through an oral opening and over the digestible parts of prey. The discovery of NO-cGMP-mediated relaxation in an echinoderm demonstrates that regulation of smooth muscle tone by this signaling pathway also occurs in animals other than vertebrates.

20.
Philos Trans R Soc Lond B Biol Sci ; 356(1407): 381-408, 2001 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-11316486

RESUMEN

The plant Cannabis sativa has been used by humans for thousands of years because of its psychoactivity. The major psychoactive ingredient of cannabis is Delta(9)-tetrahydrocannabinol, which exerts effects in the brain by binding to a G-protein-coupled receptor known as the CB1 cannabinoid receptor. The discovery of this receptor indicated that endogenous cannabinoids may occur in the brain, which act as physiological ligands for CB1. Two putative endocannabinoid ligands, arachidonylethanolamide ('anandamide') and 2-arachidonylglycerol, have been identified, giving rise to the concept of a cannabinoid signalling system. Little is known about how or where these compounds are synthesized in the brain and how this relates to CB1 expression. However, detailed neuroanatomical and electrophysiological analysis of mammalian nervous systems has revealed that the CB1 receptor is targeted to the presynaptic terminals of neurons where it acts to inhibit release of 'classical' neurotransmitters. Moreover, an enzyme that inactivates endocannabinoids, fatty acid amide hydrolase, appears to be preferentially targeted to the somatodendritic compartment of neurons that are postsynaptic to CB1-expressing axon terminals. Based on these findings, we present here a model of cannabinoid signalling in which anandamide is synthesized by postsynaptic cells and acts as a retrograde messenger molecule to modulate neurotransmitter release from presynaptic terminals. Using this model as a framework, we discuss the role of cannabinoid signalling in different regions of the nervous system in relation to the characteristic physiological actions of cannabinoids in mammals, which include effects on movement, memory, pain and smooth muscle contractility. The discovery of the cannabinoid signalling system in mammals has prompted investigation of the occurrence of this pathway in non-mammalian animals. Here we review the evidence for the existence of cannabinoid receptors in non-mammalian vertebrates and invertebrates and discuss the evolution of the cannabinoid signalling system. Genes encoding orthologues of the mammalian CB1 receptor have been identified in a fish, an amphibian and a bird, indicating that CB1 receptors may occur throughout the vertebrates. Pharmacological actions of cannabinoids and specific binding sites for cannabinoids have been reported in several invertebrate species, but the molecular basis for these effects is not known. Importantly, however, the genomes of the protostomian invertebrates Drosophila melanogaster and Caenorhabditis elegans do not contain CB1 orthologues, indicating that CB1-like cannabinoid receptors may have evolved after the divergence of deuterostomes (e.g. vertebrates and echinoderms) and protostomes. Phylogenetic analysis of the relationship of vertebrate CB1 receptors with other G-protein-coupled receptors reveals that the paralogues that appear to share the most recent common evolutionary origin with CB1 are lysophospholipid receptors, melanocortin receptors and adenosine receptors. Interestingly, as with CB1, each of these receptor types does not appear to have Drosophila orthologues, indicating that this group of receptors may not occur in protostomian invertebrates. We conclude that the cannabinoid signalling system may be quite restricted in its phylogenetic distribution, probably occurring only in the deuterostomian clade of the animal kingdom and possibly only in vertebrates.


Asunto(s)
Cannabinoides/metabolismo , Fenómenos Fisiológicos del Sistema Nervioso , Receptores de Droga/metabolismo , Transducción de Señal/fisiología , Animales , Moduladores de Receptores de Cannabinoides , Humanos , Neurobiología , Receptores de Cannabinoides , Receptores de Droga/fisiología
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