Sustainable cultivation of melon landraces: Effects of grafting on the accumulation of flavor-related compounds.

Melon landraces are highly appreciated by consumers who pay price premiums to compensate for lower yields, enabling on-farm conservation. However, they are highly susceptible to soilborne diseases. This study analyses the impact of Cucurbita and Cucumis rootstocks on the accumulation of flavor-related metabolites in Spanish landraces of the Ibericus melon group, as a strategy to promote their sustainable cultivation. Scion genotype was the main factor conditioning the accumulation of sugars and acids both under standard and saline organic farming conditions. The effects of grafting on organic acid accumulation were negligible, while the effects on sugar content were significant. The latter effects were dependent on specific scion-rootstock combinations, though wild Cucumis (e.g. Fian) rootstocks represent an alternative that should be further studied. The effect on the accumulation of volatiles was limited, and again depended on specific scion-rootstock combinations. The rootstock effect even differed between populations of the same landrace.

Physical activity guidelines and preschooler's obesity status.

AIM: The benefits of promoting physical activity (PA) in counteracting the high prevalence of childhood obesity have become increasingly important in the past decade. The aim of this study was to examine the association between compliance of daily PA recommendations and the risk of being overweight or obese in preschool-aged children. METHODS: The sample comprised 607 children aged 4-6 years, recruited from kindergartens located in the metropolitan area of Porto, Portugal. Preschooler's body mass index was classified according to International Obesity Task Force. PA was assessed during 7 consecutive days by accelerometer. Children were classified as meeting or not meeting PA recommendations based on two guidelines: (i) at least 3 h per day of total PA (TPA); and (ii) at least 1 h per day of moderate to vigorous PA (MVPA). RESULTS: The prevalence of overweight and obesity was 23.5 and 10.6% in girls and 17.2 and 8.9% in boys. In all, 90.2 and 97.3% of girls met the ≥ 1 h MVPA and ≥ 3 h TPA recommendations, respectively. In all, 96.2 and 99.4% boys met the ≥ 1 h MVPA and 3 h TPA recommendations, respectively. Boys were significantly more likely to achieve the ≥ 1 h MVPA and ≥ 3 h TPA recommendations than girls (P ≤ 0.001). Not meeting the ≥ 1 h MVPA guideline was associated with obesity status (OR: 3.8; IC: 1.3-10.4), in girls, but not boys. No other statistically significant associations were found. DISCUSSION: These findings suggest that over 90% of children met the recommended guidelines. There is an association with low levels of MVPA and higher obesity status among preschool girls. Further, longitudinal studies are needed to confirm these data.

Trichinellosis survey in the wild boar from the Toledo mountains in south-western Spain (2007-2008): molecular characterization of Trichinella isolates by ISSR-PCR.

In Spain, trichinellosis represents a public health problem, with an average of five outbreaks per year, wild boar meat being the main source of infection. A trichinellosis survey (2007-2008 hunting campaign) was carried out on wild boars in the Toledo Mountains (south-western Spain, EU) in the context of a surveillance programme on wildlife diseases. A total of 2216 wild boars from different locations of the region were examined. The examination was carried out by veterinarians in the local abattoir (Matadero Municipal de Toledo). The positive samples were sent to the Department of Parasitology (Facultad de Farmacia, UCM) for experimental isolation and specific identification by inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR). Using this technique we identified 17 isolates as Trichinella spiralis with an electrophoretic profile indistinguishable from the T. spiralis reference strain (ISS48). We confirmed that ISSR-PCR is a robust technique for the molecular identification of Trichinella isolates. According to our results, the prevalence of T. spiralis in wild boars from the Toledo Mountains (>800 m above sea level) during the hunting season was approximately 0.77%. The prevalence of T. spiralis (100% of our observations) is a good example of the persistence of this species in sylvatic conditions (coming from the domestic cycle), if a good wild host is abundant. Our observations confirm the major prevalence of T. spiralis over T. britovi in this region, as well as the risk to human health represented by the consumption of uninspected wild boar meat.

The addition of a new immunomodulator with the adjuvant adaptation ADAD system using fatty acid binding proteins increases the protection against Fasciola hepatica.

Fatty acid binding proteins (FABP) have shown protective immune response against Fasciola hepatica infection. We evaluated the protection induced by the Fh12 FABP from F. hepatica (Fh12) combined with the new immunomodulator the lipidic aminoalcohol OA0012 in the ADAD system in mice and sheep. In this work we introduced a lipidic aminoalcohol OA0012 as immunomodulator alone or in combination with the hydroalcoholic extract of Phlebodium pseudoaureum; PAL. Mice vaccinated with ADAD containing OA0012+Fh12 or OA0012+Qs+Fh12 had survival rates of 40-50%. Sheep ADAD-vaccinated with OA0012+Qs+Fh12 showed lower fluke recovery, less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Sheep ADAD-vaccinated with OA0012 combined PAL and Qs+Fh12 showed lower fluke recovery (42%), lower adult worms count (57%) lower faecal egg count (38%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the addition of a new immunomodulator of synthesis to ADAD system with FABPs increased the protection against F. hepatica.

[Robotic radical prostatectomy: overview of our learning curve]. / Prostatectomía radical robótica: revisión de nuestra curva de aprendizaje.

OBJECTIVE: We present the first cases of our robotic radical prostatectomy with Da Vinci (RRPdaV) that corresponds to the learning curve (LC) of the surgeon that has initiated with this technique. METHODS: We reviewed the first 20 patients that underwent RRPdaV, performed by an expert surgeon, without previous laparoscopic training, but with a wide experience in retropubic and perineal prostatectomy (HV). We analyzed: Surgical time, blood loss, conversion rate, intra and postoperative complications, hospital stay and days of bladder catheterization. Also: rates and location of surgical margins, as well as functional outcomes with an average follow up of 10 months. RESULTS: Mean operating time was 140 minutes (100-211) and blood loss 180 mL (80-360), and none required a blood transfusion. There were no intraoperative complications and neither any conversion to open surgery. The only postoperative outstanding fact was mean hospital stay were 3,35 days. (3-5). We had 6 cases of positive surgical margins (30%). The most frequent location was postero-lateral. Eighteen out of 20 patients (90%) were early totally continent, 2 (10%) required the use of one pad during the first six months due slight stress incontinence that stopped spontaneously. From 20 cases, two of them (10%) had preoperative erectile dysfunction; 12 out of the remaining 18 (66.6%) preserved potency at review and 6 (33.4%) had postoperative erectile dysfunction. CONCLUSIONS: It has been demonstrated that robotic surgery for radical prostatectomy is clearly an advantage technique (easy maneuver although it is a minimally invasive technique, comfortable and ergonomic position for the surgeon, 3D visualization and short learning curve). The RRPDAv learning curve is significantly shorter if the surgeon has a wide previous surgical experience in open and/or laparoscopic surgery.

[Cutaneous metastases of renal cell carcinoma]. / Metastasis cutánea de carcinoma de células renales.

Renal cell carcinoma has an unknown evolution. We report a case of a man with a skin metastases from renal cell carcinoma and an unfortunate result, five years after its radical surgical treatment. We review the literature and emphasize the need of a long and exhaustive surveillance in these patients.

[Loop diuretics and ototoxicity]. / Diuréticos del asa y ototoxicidad.

Loop diuretics are quite often used in medical practice. In spite of a wide security, there are several adverse events that should be known, in order to be early recognised as soon as they appear. Ototoxicity associated to furosemide is infrequent and reversible. However, permanent deafness associated with furosemide administration has been previously reported.

[Extraadrenal perirenal myelolipoma: report of a case and review of the literature]. / Mielolipoma extraadrenal perirenal: aportación de un caso y revisión de la literatura.

Extra-adrenal myelolipomas are rare bening tumours that are componed of mature fat cells and myeloid elements. These lesions are usually asyntomatic and often found incidentally on radiographic studies. We report a case of extra-adrenal perirenal myelolipoma.

Molecular characterization of Trichinella genotypes by inter-simple sequence repeat polymerase chain reaction (ISSR-PCR).

A bulk analysis of inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR) provides a quick, reliable, and highly informative system for DNA banding patterns that permit species identification. The present study evaluates the applicability of this system to Trichinella species identification. After a single amplification carried out on a single larva with the primer 816([CA]nRY) under high stringency conditions, which provide high reproducibility, we were able to identify by consistent banding patterns 5 sibling species: Trichinella spiralis (ISS48), 2 Trichinella britovi isolates (ISS11 and ISS86), Trichinella murrelli (ISS35), Trichinella nativa (ISS71), Trichinella nelsoni (ISS29); 3 additional Trichinella genotypes: T8 (ISS149), T9 (ISS408 and ISS409), and T6 (ISS34); and the nonencapsulated species Trichinella pseudospiralis (ISS13). Moreover, 33 new Trichinella isolates from 2 zoogeographical regions were unequivocally identified. All Trichinella isolates have shown an identical pattern with those produced by the reference strain. According to these data, we have demonstrated that ISSR-PCR is a robust technique that emerges as a useful new application for the molecular identification of Trichinella isolates in epidemiological studies.

[Early subdural haematoma as the first symptom of intracranial hypotension syndrome: results from magnetic resonance imaging]. / Hematoma subdural precoz como forma de inicio del sindrome de hipotensión intracraneal: hallazgos en resonancia magnética.

INTRODUCTION: Subdural haematoma associated to intracranial hypotension syndrome (IHS) is an infrequent complication. Its sudden early appearance in this female patient allowed us to diagnose and treat the syndrome at an early stage of development. CASE REPORT: We describe the case of a 29-year-old patient who had a caesarean with spinal anaesthesia and, 48 hours afterwards, presented IHS accompanied by focal neurological symptoms as a consequence of a subdural haematoma. Performing an emergency computerised tomography scan and magnetic resonance imaging (MRI) at 14 hours allowed early diagnosis and treatment to be established. CONCLUSIONS: MRI is essential to confirm the clinical suspicion of IHS and thus avoid the need to submit the patient to invasive tests. In this way, treatment for the IHS can be initiated at an early stage and the subdural haematoma can be resolved without the need for surgical drainage.

[Outcomes evaluation after the implementation of a pre-hospital thrombolysis protocol in rural areas]. / Evaluación de resultados tras la implantación de un protocolo de fibrinólisis extrahospitalaria en zonas rurales.

INTRODUCTION: The aim is to evaluate the outcomes obtained from the implementation of a pre-hospital thrombolysis protocol in 3 rural emergency care teams, as well as delays and strategies of reperfusion applied in the treatment of the ST-segment elevation myocardial infarction. MATERIAL AND METHODS: Retrospective cohort study (n=52) with historical control (n=20) of the patients assisted for ST-segment elevation myocardial infarction. Medical emergency care teams, hospital, computerized medical history and ARIAM register reports were revised, obtaining epidemiological and clinical features, off-hospital management, reperfusion, time intervals and mortality. RESULTS: The baseline features in both groups were not significantly different. There was a non-significant improvement of emergency care teams-hospital diagnostic concordance (85.3 versus 76.9%). We found a similar use of nitroglycerin, morphine and aspirin; significant increase (P<0.0001) of clopidogrel/prasugrel (55 versus 90.4%) and enoxaparin/fondaparinux (35 versus 76.9%), as well as pre-hospital thrombolysis (5 versus 30,8%, P<0.03), that was applied within the first 2h to 71.4%, with a median door-needle of 40min, whereas in-hospital thrombolysis and primary angioplasty were performed after 3h from the symptoms onset (P<0.01). Delays are associated with the patient's own lateness (P<0.02). Pharmaco-invasive strategy increases (62.5 versus 84.6%) more than primary angioplasty (15 versus 17.3%), reducing in-hospital thrombolysis (35 versus 19.2%), all of them non-significant. Complications are similar and one-year mortality is reduced (P<0.67). CONCLUSIONS: The protocol is effective, safe, and reliable. It reduces delays and improves pre-hospital attention. The pharmaco-invasive strategy is a valid option.

Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats.

We have recently found that cannabinoid receptor binding and gene expression markedly decreased in extrapyramidal structures of aged rats. The present study was designed to analyze the possible existence of similar aging-induced changes in cannabinoid receptor binding and gene expression in brain regions other than extrapyramidal areas, but that also contain a significant population of cannabinoid receptors, such as the cerebellum, hippocampal structures, limbic and hypothalamic nuclei, the cerebral cortex and others. To this end, we analyzed cannabinoid receptor binding, using autoradiography, and cannabinoid receptor mRNA levels, using in situ hybridization, in slide-mounted brain sections obtained from young (3 month old) and aged (> 2 year old) rats. Results were as follows. In the cerebellum, aged rats exhibited a marked decrease in cannabinoid receptor binding in the molecular layer (-33.3%), although accompanied by no changes in mRNA levels in the granular layer. In the cerebral cortex, a small, although statistically significant, decrease in binding was found in the deep layer (VI) (-18.3%) of aged rats, whereas no changes were found in the superficial layer (I). As in the case of the cerebellum, mRNA levels did not change in the cerebral cortex layers (II-III and V-VI). The different regions of the Ammon's horn of the hippocampus exhibited similar cannabinoid receptor binding levels in aged and young rats. Interestingly, mRNA levels decreased in aged rats to a small, but statistically significant, extent (CA1: -26.1%; CA2: -21.6%; CA3: -14.4%). This was also seen in another hippocampal structure, the dentate gyrus (-14.6%), although in this region binding levels increased in aged rats (+28.4%). Two hypothalamic structures, the arcuate nucleus and the ventromedial hypothalamic nucleus, exhibited decreased cannabinoid receptor binding in aged rats (-31.1% and -30.3%, respectively), but this was not seen in the medial preoptic area. This was accompanied by no changes in mRNA levels in the ventromedial hypothalamic nucleus. In the limbic structures, aged rats exhibited similar binding levels to young rats. This was seen in the nucleus accumbens, septum nuclei and basolateral amygdaloid nucleus. However, mRNA levels slightly decreased in the basolateral amygdaloid nucleus (-13.4%), whereas they were not altered in the septum nuclei. Finally, other brain structures, such as the central gray substance and the brainstem, exhibited similar binding levels in aged and young rats. However, it is important to note that mRNA levels increased significantly (+211.2%) in the brainstem of aged rats, an area where the levels of binding and mRNA were very low in young rats. This marked increase may be related to an increase in the presence of glial elements in this region, as revealed by the increase in the immunoreactivity for glial fibrillary acidic protein observed in the brainstem of aged rats as compared to young animals. In summary, senescence was associated with changes in cannabinoid receptors in the cerebellum, the cerebral cortex, limbic and hypothalamic structures, the hippocampus and other brain regions. However, the changes observed (i) were not as marked and relevant as those early reported in extrapyramidal areas, and (ii) exhibited regional differences that might be attributed to the different roles played by these receptors in each region. Of particular relevance by their magnitude were the aging-induced decrease in binding found in the cerebellum and the hypothalamus, and the increase in mRNA levels observed in the brainstem. The latter might be related to an increase in the presence of glial cells which might contain cannabinoid receptor mRNA.

Pharmacological and biochemical interactions between opioids and cannabinoids.

Opioids and cannabinoids are among the most widely consumed drugs of abuse in humans. A number of studies have shown that both types of drugs share several pharmacological properties, including hypothermia, sedation, hypotension, inhibition of both intestinal motility and locomotor activity and, in particular, antinociception. Moreover, phenomena of cross-tolerance or mutual potentiation of some of these pharmacological effects have been reported. In recent years, these phenomena have supported the possible existence of functional links in the mechanisms of action of both types of drugs. The present review addresses the recent advances in the study of pharmacological interactions between opioids and cannabinoids, focusing on two aspects: antinociception and drug addiction. The potential biochemical mechanisms involved in these pharmacological interactions are also discussed together with possible therapeutic implications of opioid-cannabinoid interactions.

Effect of piroxicam, metamizol, and S-adenosylmethionine in a murine model of experimental trichomoniasis.

Biological effects of piroxicam, metamizol, and S-adenosylmethionine (S-AMET) have been tested in NMRI mice infected intraperitoneally with Trichomonas vaginalis. An intraperitoneal treatment during ten preinfection days with piroxicam (10 mg/Kg/day), or metamizol (275 mg/Kg/day), but not with S-AMET (117 mg/Kg/day) induced a significant decrease of abdominal lesions and mortality, assessed by means of a pathogenicity index. The trichomonicidal activity of piroxicam, metamizol, and S-AMET was tested in vitro at the concentration of 300 microM, but found ineffective. These assays have shown the usefulness of the experimental trichomoniasis model for the study of the immunomodulating activity of synthetic drugs.

Sex- and age-related changes in catecholamine metabolism and release of rat adrenal gland.

To examine the possible existence of changes in the adrenal catecholaminergic activity during aging, we analyzed the adrenal content of catecholamines (CA) and the activities of selected enzymes involved in their metabolism as well as the basal and the K+-stimulated release of these CA in incubated adrenal tissue of aged (greater than 22 months) and young (2 months) rats of both sexes. Adrenal contents of norepinephrine (NE) and epinephrine (E) of male rats were unaltered in aging, although aged males showed an increased activity of tyrosine hydroxylase (TH) and a decrease in phenylethanolamine-N-methyl transferase (PNMT) activity. In addition, the in vitro release of both CA as well as their content in the incubated adrenal tissue were higher in aged males than in young animals. However, the response of the adrenal of aged males to incubation with stimulatory concentrations of K+ was significantly lower than that observed in young males. Aged females showed increases in the adrenal content of E, although the activities of TH and PNMT were unaltered. As in aged males, the in vitro release of CA from incubated adrenal tissue was higher in aged females than in young rats, but the CA amounts measured in the incubated tissues were similar. Moreover, the response to stimulatory concentrations of K+ was lower in aged females than in young animals. In summary, these results clearly indicate that adrenal catecholaminergic activity is enhanced during aging, which could have important consequences for physiological functions regulated by the adrenal secretion. Also, some differences in the effects of aging could be observed between males and females.

The endocannabinoid system and Huntington's disease.

The research in Huntington's disease (HD) has been growing exponentially during the last decade, since the discovery of the genetic basis that leads to neurodegeneration. HD is one of several progressive neurodegenerative disorders, in which the underlying mutation is a CAG expansion encoding a polyglutamine tract in a specific protein, which in the case of HD, is called huntingtin. The first clinical symptoms of HD are generally psychiatric abnormalities, most commonly depression and mood disturbances. Involuntary choreiform movements and dementia develop over the next 15-20 years, and death generally results from complications derived from immobility. There is currently no cure, or even an effective therapy to offset the decline in mental and motor capabilities suffered by those affected by HD, but recent studies have started to examine the usefulness of different classes of new compounds. Among these, plant-derived, synthetic or endogenous cannabinoids have been proposed to have therapeutic value for the treatment of HD, since they act on cannabinoid CB(1) receptors located in the basal ganglia circuitry, that is affected by the striatal atrophy typical of HD. Recent studies have characterized the changes in these receptors, as well as their endogenous ligands, in the basal ganglia in a variety of animal models of HD. The results are indicative that the endocannabinoid system becomes hypofunctional in this disease, which could be related to the hyperkinesia typical of the earliest phases of this disease. In addition, it has been proposed that the loss of these receptors might be involved in the process of pathogenesis itself. This, together with the well-known protective properties of cannabinoid-related compounds, suggest that, in addition to a symptomatic usefulness, cannabinoids might also serve to delay or to arrest the development of this disease. The present article will review all recent data dealing with the biochemical, pharmacological and therapeutic bases that support a potential role of cannabinoids in the pathogenesis and/or therapeutic treatment of this motor disorder.

Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons.

The changes induced by maternal exposure to cannabinoids in the maturation of nigrostriatal, tuberoinfundibular and mesolimbic dopaminergic activities of rat offspring 15-40 days old were studied. In the striatum, tyrosine hydroxylase activity was constantly decreased during cannabinoid exposure in males. This decrease was correlative to increased number of D1 and D2 dopaminergic receptors. Both effects were also observed after the drug withdrawal caused by weaning on day 24. In females, the most consistent effect appeared on day 20, when decreased dopamine content and number of D1 receptors were observed. Both effects disappeared after drug withdrawal, but the reduction in the number of D1 receptors was again observed 40 days after birth. In the limbic area, cannabinoid exposure caused a decrease in the number of D1 receptors in 15-day-old females, along with decreases in the content of dopamine and its metabolite, L-3,4-dihydroxyphenylacetic acid. Changes in receptors disappeared on subsequent days, but increases in L-3,4-dihydroxyphenylacetic acid content and in its ratio with dopamine (L-3,4-dihydroxyphenylacetic acid/dopamine) were observed on day 20 followed by a decrease in the neurotransmitter content on day 30. In males, tyrosine hydroxylase activity increased on day 30, followed by an increase in L-3,4-dihydroxyphenylacetic acid content and L-3,4-dihydroxyphenylacetic acid/dopamine ratio on day 40. In the hypothalamus, the cannabinoid effects were always manifested after the cessation of drug exposure. Thus, a rise in L-3,4-dihydroxyphenylacetic acid/dopamine ratio was observed in 30-day-old females, and it was followed by a decrease on day 40, accompanied by a decrease in the anterior pituitary content of dopamine. Rise in prolactin release was not significant. In males, tyrosine hydroxylase activity was increased 30 days after birth, while L-3,4-dihydroxyphenylacetic acid content decreased. On day 40, L-3,4-dihydroxyphenylacetic acid content increased, paired to a rise in L-3,4-dihydroxyphenylacetic acid/dopamine ratio and anterior pituitary content of dopamine and to a decrease in the prolactin release. Perinatal exposure to cannabinoids altered the normal development of nigrostriatal, mesolimbic and tuberoinfundibular dopaminergic neurons, as reflected by changes in several indices of their activity. These changes were different regarding the sex and brain areas. Cannabinoid effects were more marked and constant in the striatum of males, while alterations in limbic neurons were mostly transient and those in hypothalamic neurons occurred after drug withdrawal. A long-term impact of these early changes on the neurological processes of adulthood is plausible.

Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35S]guanylyl-5'O-(thio)-triphosphate binding in the basal ganglia of aged rats.

Recent reports have demonstrated that cannabinoid receptor binding decreases in several neurodegenerative diseases related to extrapyramidal function. However, there is little evidence with regard to potential changes of these receptors during senescence. The present study was designed to determine the possible existence of ageing-induced changes in cannabinoid receptor binding and gene expression in extrapyramidal areas. To this end, we analysed cannabinoid receptor binding and basal and cannabinoid receptor agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate binding, by using autoradiography, and cannabinoid receptor messenger RNA levels, by using in situ hybridization, in slide-mounted brain sections obtained from young (three-month-old) and aged (>two-year-old) rats. Results were as follows. Aged rats exhibited a marked decrease in cannabinoid receptor binding in most of the basal ganglia, excepting the globus pallidus which had similar binding levels in both young and aged rats. The highest decreases were in the entopeduncular nucleus (-49.6%) and substantia nigra pars reticulata (-45.2%), whereas more moderate decreases were found in the lateral caudate putamen (-29%) and only a decremental trend in the medial caudate putamen (-13.1%). These decreases in cannabinoid receptor binding were paralleled by less marked increases in WIN 55212-2-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate binding in these structures in aged rats (% of agonist stimulation: 189% in the substantia nigra; 29.4% in the lateral caudate putamen) as compared to young rats (296% and 53.2%, respectively). Contrarily, the percentage of agonist stimulation was similar in the globus pallidus, an area where cannabinoid receptor binding did not change during ageing, of aged (205.5%) and young (215.5%) rats. In addition, aged rats also exhibited significant reductions in the cannabinoid receptor messenger RNA levels in the medial (-14.3%) and, in particular, in the lateral (-29.4%) caudate putamen, the area where the cell bodies of cannabinoid receptor-containing neurons, projecting to the substantia nigra, entopeduncular nucleus and globus pallidus, are located. In summary, the synthesis and binding levels of cannabinoid receptors markedly dropped in different structures of the extrapyramidal system of aged rats. Since these receptors, located in the basal ganglia, seem to play a role in motor control, this loss of cannabinoid receptors might be related to the motor impairment which progressively appears during senescence.

Effects of cannabinoids on adrenaline release from adrenal medullary cells.

1. The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells. 2. In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 microg x kg(-1)) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB1 cannabinoid receptor antagonist SR141716A (500 microg x kg(-1)). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration. 3. In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 microM) and this effect was antagonized by SR141716A (1 microM). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 microM) and muscarinic (by atropine 0.5 microM) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 microM) had no effect on adrenaline release. 4. No detectable specific CB1 receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization. 5. The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits.

Possible role of dopamine and noradrenaline in the regulation of prolactin secretion from an ectopic anterior pituitary gland in female rats.

It was recently reported that anterior pituitary tissue transplanted to an ectopic site contains measurable amounts of dopamine and noradrenaline. To examine the possibility of local catecholaminergic control of prolactin secretion from ectopic pituitaries, pituitary grafted and sham-operated female rats were submitted to several pharmacological treatments modifying catecholamine synthesis. Administration of a single dose of alpha-methyl-p-tyrosine (alpha-MPT) significantly reduced dopamine content in the graft, while noradrenaline content was not modified. Similar changes in the contents of dopamine and noradrenaline after alpha-MPT administration were observed in the hypothalamus and in the in-situ pituitary in both grafted and sham-operated rats. Plasma concentrations of prolactin were increased in both grafted and sham-operated rats after administration of alpha-MPT. A single injection of L-3,4-dihydroxyphenylalanine (L-DOPA) increased dopamine content in the ectopic pituitary gland without altering the noradrenaline content, and produced similar effects in the hypothalamus and in-situ pituitary of grafted and control rats. Plasma prolactin concentrations were decreased by L-DOPA in both pituitary grafted and control rats. Administration of DL-treo-dihydroxyphenylserine (DOPS) increased noradrenaline content in the ectopic pituitary and reduced plasma prolactin concentrations in pituitary grafted rats. In contrast, injection of DOPS to control rats increased both hypothalamic noradrenaline content and plasma prolactin concentrations. These results suggest that dopamine and noradrenaline present in the ectopic pituitary tissue have a role in mediating prolactin release from pituitary transplants.