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1.
Am J Physiol Regul Integr Comp Physiol ; 314(2): R242-R251, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29046317

ABSTRACT

Nitrite ([Formula: see text]) causes vasodilation in mammals due to the formation of (nitric oxide) NO by endogenous [Formula: see text] reduction in the vascular wall. In this study, we determined if a similar mechanism operates in amphibians. Dual-wire myography of the iliac artery from Rhinella marina showed that applied [Formula: see text] caused a concentration-dependent vasodilation in normoxia (21% O2; EC50: 438 µM). Hypoxia (0.63% O2) significantly increased the maximal dilation to [Formula: see text] by 5% ( P = 0.0398). The addition of oxyhemoglobin significantly increased the EC50 ( P = 0.0144; EC50: 2,236 µM) but did not affect the maximal vasodilation. In contrast, partially deoxygenated hemoglobin (90% desaturation) did not affect the EC50 ( P = 0.1189) but significantly ( P = 0.0012) increased the maximal dilation to [Formula: see text] by 11%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) completely abolished the response to [Formula: see text] ( P < 0.0001), and of the nitric oxide synthase inhibitors, only N5-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO; P = 0.0028) significantly reduced the [Formula: see text] vasodilation. The xanthine oxidoreductase inhibitor allopurinol ( P = 0.927), the nitric oxide-scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (C-PTIO; P = 0.478), and disruption of the endothelium ( P = 0.094) did not affect the [Formula: see text] vasodilation. Incubation of iliac arteries with 1 mM [Formula: see text] did not a cause a change in the cGMP concentration (P = 0.407). Plasma [Formula: see text] was found to be 0.86 ± 0.20 µmol/l, while nitrate ([Formula: see text]) was 19.55 ± 2.55 µmol/l. Both cygb and ngb mRNAs were expressed in the iliac artery, and it is possible that these globins facilitate [Formula: see text] reduction in hypoxia. In addition, [Formula: see text] intracellular disproportionation processes could be important in the generation of NO from [Formula: see text].


Subject(s)
Iliac Artery/drug effects , Sodium Nitrite/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Amphibian Proteins/genetics , Amphibian Proteins/metabolism , Animals , Bufo marinus , Cytoglobin/genetics , Cytoglobin/metabolism , Female , Hemoglobins/metabolism , Iliac Artery/metabolism , In Vitro Techniques , Male , Neuroglobin/genetics , Neuroglobin/metabolism , Nitric Oxide/metabolism , Nitrite Reductases/metabolism , Oxidation-Reduction , Oxyhemoglobins/metabolism , Sodium Nitrite/metabolism , Vasodilator Agents/metabolism
2.
Am J Physiol Regul Integr Comp Physiol ; 315(2): R380-R396, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29668323

ABSTRACT

Selenoprotein S (Seps1) is an endoplasmic reticulum (ER) resident antioxidant implicated in ER stress and inflammation. In human vastus lateralis and mouse hindlimb muscles, Seps1 localization and expression were fiber-type specific. In male Seps1+/- heterozygous mice, spontaneous physical activity was reduced compared with wild-type littermates ( d = 1.10, P = 0.029). A similar trend was also observed in Seps1-/- knockout mice ( d = 1.12, P = 0.051). Whole body metabolism, body composition, extensor digitorum longus (EDL), and soleus mass and myofiber diameter were unaffected by genotype. However, in isolated fast EDL muscles from Seps1-/- knockout mice, the force frequency curve (FFC; 1-120 Hz) was shifted downward versus EDL muscles from wild-type littermates ( d = 0.55, P = 0.002), suggestive of reduced strength. During 4 min of intermittent, submaximal (60 Hz) stimulation, the genetic deletion or reduction of Seps1 decreased EDL force production ( d = 0.52, P < 0.001). Furthermore, at the start of the intermittent stimulation protocol, when compared with the 60-Hz stimulation of the FFC, EDL muscles from Seps1-/- knockout or Seps1+/- heterozygous mice produced 10% less force than those from wild-type littermates ( d = 0.31, P < 0.001 and d = 0.39, P = 0.015). This functional impairment was associated with reduced mRNA transcript abundance of thioredoxin-1 ( Trx1), thioredoxin interacting protein ( Txnip), and the ER stress markers Chop and Grp94, whereas, in slow soleus muscles, Seps1 deletion did not compromise contractile function and Trx1 ( d = 1.38, P = 0.012) and Txnip ( d = 1.27, P = 0.025) gene expression was increased. Seps1 is a novel regulator of contractile function and cellular stress responses in fast-twitch muscles.


Subject(s)
Endoplasmic Reticulum/enzymology , Membrane Proteins/deficiency , Muscle Contraction , Muscle Fibers, Fast-Twitch/enzymology , Muscle Strength , Selenoproteins/deficiency , Adult , Animals , Body Composition , Carrier Proteins/genetics , Carrier Proteins/metabolism , Electric Stimulation , Endoplasmic Reticulum Stress , Hindlimb , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Motor Activity , Muscle Fibers, Slow-Twitch/enzymology , Selenoproteins/genetics , Selenoproteins/metabolism , Thioredoxins/genetics , Thioredoxins/metabolism , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism , Young Adult
3.
Cell Tissue Res ; 366(3): 679-692, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27543051

ABSTRACT

In mammals, nitric oxide (NO) produced by nitric oxide synthase 3 (NOS3) localised in vascular endothelial cells is an important vasodilator but the presence of NOS3 in the endothelium of amphibians has been concluded to be absent, based on physiological studies. In this study, a nos3 cDNA was sequenced from the toad, Rhinella marina. The open reading frame of R. marina nos3 encoded an 1170 amino acid protein that showed 81 % sequence identity to the recently cloned Xenopus tropicalis nos3. Rhinella marina nos3 mRNA was expressed in a range of tissues and in the dorsal aorta and pulmonary, mesenteric, iliac and gastrocnemius arteries. Furthermore, nos3 mRNA was expressed in the aorta of Xenopus laevis and X. tropicalis. Quantitative real-time PCR showed that removal of the endothelium of the lateral aorta of R. marina significantly reduced the expression of nos3 mRNA compared to control aorta with the endothelium intact. However, in situ hybridisation was not able to detect any nos3 mRNA in the dorsal aorta of R. marina. Immunohistochemistry using a homologous R. marina NOS3 antibody showed immunoreactivity (IR) within the basal region of many endothelial cells of the dorsal aorta and iliac artery. NOS3-IR was also observed in the proximal tubules and collecting ducts of the kidney but not within the capillaries of the glomeruli. This is the first study to demonstrate that vascular endothelial cells of an amphibian express NOS3.


Subject(s)
Amphibians/metabolism , Blood Vessels/enzymology , Nitric Oxide Synthase Type III/metabolism , Amino Acid Sequence , Animals , Blotting, Northern , Female , Gene Expression Profiling , Gene Expression Regulation , In Situ Hybridization , Male , Nitric Oxide Synthase Type III/chemistry , Nitric Oxide Synthase Type III/genetics , Organ Specificity/genetics , Phylogeny , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, Protein
4.
J Mol Endocrinol ; 71(4)2023 11 01.
Article in English | MEDLINE | ID: mdl-37675942

ABSTRACT

A deficiency in hydrogen sulfide has been implicated in the development and progression of diabetic chronic kidney disease. The purpose of this study was to determine the effect of diabetes on the H2S system in early-stage diabetic kidney disease. We characterised gene and protein expression profile of the enzymes that regulate H2S production and degradation, and H2S production capacity, in the kidney from 10-week-old C57BL6Jdb/db mice (n = 6), in age-matched heterozygous controls (n = 7), and in primary endothelial cells (HUVECs) exposed to high glucose. In db/db mice, renal H2S levels were significantly reduced (P = 0.009). Protein expression of the H2S production enzymes was differentially affected by diabetes: cystathionine ß-synthase (CBS) was significantly lower in both db/db mice and high glucose-treated HUVECs (P < 0.0001; P = 0.0318) whereas 3-mercatopyruvate sulfurtransferase (3-MST) expression was higher in the db/db kidney (P < 0.0001), yet lower in the HUVECs (P = 0.0001). Diabetes had no effect on the expression of cystathionine γ-lyase (CSE) in the db/db kidney (P = ns) but was associated with reduced expression in the HUVECs (P = 0.0004). Protein expression of degradation enzyme sulfide quinone reductase (SQOR) was significantly higher in db/db kidney (P = 0.048) and lower in the high glucose-treated HUVECs (P = 0.008). Immunofluorescence studies revealed differential localisation of the H2S enzymes in the kidney, including both tubular and vascular localisation, suggestive of functionally distinct actions in the kidney. The results of this study provide foundational knowledge for future research looking at the H2S system in both kidney physiology and the aetiology of chronic diabetic kidney disease.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Hydrogen Sulfide , Mice , Animals , Hydrogen Sulfide/pharmacology , Hydrogen Sulfide/metabolism , Diabetic Nephropathies/etiology , Endothelial Cells/metabolism , Kidney/metabolism , Glucose
5.
Biomolecules ; 10(3)2020 03 07.
Article in English | MEDLINE | ID: mdl-32156081

ABSTRACT

Aberrant extracellular matrix synthesis and remodeling contributes to muscle degeneration and weakness in Duchenne muscular dystrophy (DMD). ADAMTS-5, a secreted metalloproteinase with catalytic activity against versican, is implicated in myogenesis and inflammation. Here, using the mdx mouse model of DMD, we report increased ADAMTS-5 expression in dystrophic hindlimb muscles, localized to regions of regeneration and inflammation. To investigate the pathophysiological significance of this, 4-week-old mdx mice were treated with an ADAMTS-5 monoclonal antibody (mAb) or IgG2c (IgG) isotype control for 3 weeks. ADAMTS-5 mAb treatment did not reduce versican processing, as protein levels of the cleaved versikine fragment did not differ between hindlimb muscles from ADAMTS-5 mAb or IgG treated mdx mice. Nonetheless, ADAMTS-5 blockade improved ex vivo strength of isolated fast extensordigitorumlongus, but not slow soleus, muscles. The underpinning mechanism may include modulation of regenerative myogenesis, as ADAMTS-5 blockade reduced the number of recently repaired desmin positive myofibers without affecting the number of desmin positive muscle progenitor cells. Treatment with the ADAMTS-5 mAb did not significantly affect makers of muscle damage, inflammation, nor fiber size. Altogether, the positive effects of ADAMTS-5 blockade in dystrophic muscles are fiber-type-specific and independent of versican processing.


Subject(s)
ADAMTS5 Protein/antagonists & inhibitors , Antibodies, Monoclonal/pharmacology , Muscle Fibers, Fast-Twitch/metabolism , Muscle Strength/drug effects , Muscular Dystrophy, Duchenne/metabolism , ADAMTS5 Protein/metabolism , Animals , Disease Models, Animal , Hindlimb/metabolism , Hindlimb/pathology , Mice , Mice, Inbred mdx , Muscle Fibers, Fast-Twitch/pathology , Muscular Dystrophy, Duchenne/pathology
7.
Evolution ; 2018 Jun 19.
Article in English | MEDLINE | ID: mdl-29920667

ABSTRACT

Light environments critically impact species that rely on vision to survive and reproduce. Animal visual systems must accommodate changes in light that occur from minutes to years, yet the mechanistic basis of their response to spectral (color) changes is largely unknown. Here, we used a laboratory experiment where replicate guppy populations were kept under three different light environments for up to 8-12 generations to explore possible differences in the expression levels of nine guppy opsin genes. Previous evidence for opsin expression-light environment "tuning" has been either correlative or focused exclusively on the relationship between the light environment and opsin expression over one or two generations. In our multigeneration experiment, the relative expression levels of nine different guppy opsin genes responded differently to light environment changes: some did not respond, while others differed due to phenotypic plasticity. Moreover, for the LWS-1 opsin we found that, while we observed a wide range of plastic responses under different light conditions, common plastic responses (where the population replicates all followed the same trajectory) occurred only after multigenerational exposure to different light environments. Taken together this suggests that opsin expression plasticity plays an important role in light environment "tuning" in different light environments on different time scales, and, in turn, has important implications for both visual system function and evolution.

8.
J Comp Physiol B ; 185(2): 153-71, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25502832

ABSTRACT

Nitric oxide is one of the most important signalling molecules involved in the regulation of physiological function. It first came to prominence when it was discovered that the vascular endothelium of mammals synthesises and releases nitric oxide (NO) to mediate a potent vasodilation. Subsequently, it was shown that NO is synthesised in the endothelium by a specific isoform of nitric oxide synthase (NOS) called NOS3. Following this discovery, it was assumed that an endothelial NO/NOS3 system would be present in all vertebrate blood vessels. This review will discuss the latest genomic, anatomical and physiological evidence which demonstrates that an endothelial NO/NOS3 signalling is not ubiquitous in non-mammalian vertebrates, and that there have been key evolutionary steps that have led to the endothelial NO signalling system being a regulatory system found only in reptiles, birds and mammals. Furthermore, the emerging role of nitrite as an endocrine source of NO for vascular regulation is discussed.


Subject(s)
Blood Vessels/enzymology , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide/metabolism , Vertebrates/blood , Animals , Evolution, Molecular , Phylogeny , Reactive Oxygen Species/metabolism , Signal Transduction , Vertebrates/classification , Vertebrates/metabolism
9.
J Comp Physiol B ; 184(4): 437-47, 2014 May.
Article in English | MEDLINE | ID: mdl-24604294

ABSTRACT

Although spiny rock lobster (Jasus edwardsii) is a wholly sub-littoral species, they show a considerable ability to survive prolonged emersion, a fact exploited during the commercial export of this species. Yet, despite this remarkable hardiness, basic information on how this species responds physiologically to emersion is somewhat lacking. Using flow-through respirometry and electrophysiological techniques, we identified that J. edwardsii undergoes marked physiological changes during rest, emersion and recovery over a broad range of temperatures (3.7-17.8 °C). Under resting conditions, routine metabolic rates (RMR) were 22.57 ± 2.39, 9.69 ± 0.55 and 8.09 ± 0.27 mL O2 h(-1), average heart rates (Hr) were 54.72 ± 4.46, 37.68 ± 2.86 and 29.67 ± 0.59 BPM, and ventilation frequencies were 83.71 ± 5.86, 45.34 ± 2.91 and 41.62 ± 0.65 BPM at 15.0, 7.5 and 3.7 °C, respectively. Notably, the surgical implantation of electrodes elevated RMR compared with non-surgical treatments. In surgery and non-surgery groups, Q 10 was calculated to be ca. 3.0. Upon emersion, rate of oxygen consumption and Hr decreased below resting rates in a temperature-dependent manner, but, along with rate of CO2 production, increased steadily during 24-h emersion. Ventilation frequencies upon emersion showed a contrasting response and increased significantly above resting rates. When returned to flow-through sea water for recovery, elevated respiration rates provided clear evidence of an O2 debt, and near-complete recovery was observed after 17 h at both 15.0 and 7.5 °C, but close to no debt was recovered at 3.7 °C. In addition, J. edwardsii was observed to undergo marked diurnal and periodic ventilation cycles, characterised by synchronous changes in RMR, Hr and ventilation frequency.


Subject(s)
Palinuridae/physiology , Temperature , Animals , Basal Metabolism/physiology , Cardiovascular Physiological Phenomena , Male , Recovery of Function/physiology , Respiratory Physiological Phenomena , Rest/physiology
10.
Article in English | MEDLINE | ID: mdl-19720158

ABSTRACT

The effects of hydrogen sulphide (H(2)S) and isoeugenol exposure on activity, oxygen consumption (VO(2)), ventilation frequency (Vf) and cytochrome c oxidase activity in a teleost fish are reported. In H(2)S (200 microM Na(2)S) exposed animals VO(2) and Vf decreased significantly (both to 40% of resting) after 30 min, concurrent with a loss of equilibrium and narcosis. Post-flushing, VO(2) increased to resting values, but Vf remained depressed (P<0.05) until 30 min of recovery. Subsequently, equilibrium and mobility were regained accompanied by increases in VO(2) (66%) and Vf (15%) between 60-70 min of recovery. Isoeugenol (0.011 g L(-1)) exposed fish reached stage 4-5 of anaesthesia accompanied by decreases (P<0.05) in VO(2) (64%) and Vf (38%) by 35 min. Post-flushing, VO(2) and Vf recovered to resting values, followed by a rise (P<0.05) in VO(2) (45%) and Vf (25%). Overall, VO(2) in relation to the resting rate was reduced in isoeugenol treated animals. Conversely, VO(2) was increased (P<0.05) relative to the resting rate in H(2)S exposed fish. 20 and 200 microM Na(2)S reduced cytochrome c oxidase activity (P<0.05) in skeletal muscle and gill lamellae by between 69 and 97%, while isoeugenol had no effect in any tissue.


Subject(s)
Anesthetics/pharmacology , Electron Transport Complex IV/metabolism , Eugenol/analogs & derivatives , Gills/drug effects , Hydrogen Sulfide/pharmacology , Muscle, Skeletal/drug effects , Oxygen Consumption/drug effects , Perciformes/metabolism , Pulmonary Ventilation/drug effects , Respiratory Mechanics/drug effects , Animals , Consciousness/drug effects , Eugenol/pharmacology , Female , Gills/enzymology , Male , Muscle, Skeletal/enzymology , Stupor/chemically induced , Time Factors
11.
J Comp Physiol B ; 180(5): 715-29, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20198373

ABSTRACT

We present evidence that oxygen consumption (VO2) is oxygen partial pressure (PO2)dependent in striated muscles and PO2-independent in the vasculature in representatives of three craniate taxa: two teleost fish, a hagfish and a rat. Blood vessel VO2 displayed varying degrees of independence in a PO2 range of 15-95 mmHg, while VO2 by striated muscle tissue slices from all species related linearly to PO2 between 0 and 125 mmHg, despite VO2 rates varying greatly between species and muscle type. In salmon red muscle, lactate concentrations fell in slices incubated at a PO2 of either 30 or 100 mmHg, suggesting aerobic rather than anaerobic metabolism. Consistent with this finding, potential energy, a proxy of ATP turnover, was PO2-dependent. Our data suggest that the reduction in VO2 with falling PO2 results in a decrease in ATP demand, suggesting that the hypoxic signal is sensed and cellular changes effected. Viability and diffusion limitation of the preparations were investigated using salmon cardiac and skeletal muscles. Following the initial PO2 depletion, reoxygenation of the Ringer bathing salmon cardiac muscle resulted in VO2S that was unchanged from the first run. VO2 increased in all muscles uncoupled with p-trifluoromethoxylphenyl-hydrazone (FCCP) and 2,4-dinitrophenol (DNP). Mitochondrial succinate dehydrogenase activity, quantified by reduction of 3-(4,5-dimethylthiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan, was constant over the course of the experiment. These three findings indicate that the tissues remained viable over time and ruled out diffusion-limitation as a constraint on VO2.


Subject(s)
Energy Metabolism/physiology , Muscles/metabolism , Oxygen/metabolism , 2,4-Dinitrophenol/pharmacology , Animals , Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology , Female , Glycogen/metabolism , Hagfishes/metabolism , Heme/metabolism , Hypoxia/metabolism , Liver/metabolism , Male , Mitochondria, Muscle/enzymology , Muscles/drug effects , Myoglobin/metabolism , Oxygen/pharmacology , Oxygen Consumption/drug effects , Partial Pressure , Perciformes/metabolism , Rats , Salmon/metabolism , Succinate Dehydrogenase/metabolism
12.
J Comp Physiol B ; 179(3): 359-68, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19066910

ABSTRACT

An isolated, perfused salmon tail preparation showed oxyconformance at low oxygen delivery rates. Addition of pig red blood cells to the perfusing solution at a haematocrit of 5 or 10% allowed the tail tissues to oxyregulate. Below ca. 60 ml O(2) kg(-1) h(-1) of oxygen delivery (DO(2)), VO(2) was delivery dependent. Above this value additional oxygen delivery did not increase VO(2) of resting muscle above ca. 35 ml O(2) kg(-1) h(-1). Following electrical stimulation, VO(2) increased to ca. 65 ml O(2) kg(-1) h(-1), with a critical DO(2) of ca. 150 ml O(2) kg(-1) h(-1). Dorsal aortic pressure fell to 69% of the pre-stimulation value after 5 min of stimulation and to 54% after 10 min. Microspheres were used to determine blood flow distribution (BFD) to red (RM) and white muscle (WM) within the perfused myotome. Mass specific BFD ratio at rest was found to be 4.03 +/- 0.49 (RM:WM). After 5 min of electrical stimulation the ratio did not change. Perfusion with saline containing the tetrazolium salt 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) revealed significantly more mitochondrial activity in RM. Formazan production from MTT was directly proportional to time of perfusion in both red and WM. The mitochondrial activity ratio (RM:WM) did not change over 90 min of perfusion.


Subject(s)
Mitochondria/metabolism , Muscle, Skeletal/blood supply , Oxygen Consumption/physiology , Oxygen/metabolism , Salmon/physiology , Tail/physiology , Analysis of Variance , Animals , Blood Pressure , Electric Stimulation , Microspheres , New Zealand , Regional Blood Flow , Tail/blood supply , Tetrazolium Salts , Thiazoles
13.
J Exp Biol ; 211(Pt 14): 2205-13, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18587114

ABSTRACT

Hydrogen sulfide (H(2)S) has been proposed to mediate hypoxic vasoconstriction (HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H(2)S. Here we examined the relationship between H(2)S and O(2) in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H(2)S (Na(2)S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries (EBA) but did not affect ventral aortas or afferent branchial arteries; effects similar to those produced by hypoxia. Sensitivity of H(2)S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H(2)S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H(2)S-synthesizing enzyme, cystathionine beta-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine lambda-lyase. Oxygen consumption (M(O(2))) of hagfish DA was constant between 15 and 115 mmHg P(O(2)) (1 mmHg=0.133 kPa), decreased when P(O(2)) <15 mmHg, and increased after P(O(2)) exceeded 115 mmHg. 10 micromol l(-1) H(2)S increased and > or =100 micromol l(-1) H(2)S decreased M(O(2)). Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased M(O(2)). These results show that H(2)S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H(2)S was enhanced at low P(O(2)), it is unlikely that H(2)S contractions are mediated by either H(2)S-NO interaction or an oxidation product of H(2)S. These experiments also provide additional support for the hypothesis that the metabolism of H(2)S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle.


Subject(s)
Aorta/metabolism , Constriction, Pathologic/chemically induced , Hagfishes/physiology , Hydrogen Sulfide/pharmacology , Oxygen/pharmacology , Animals , Aorta/drug effects , Arteries/drug effects , Carbachol/pharmacology , Cardiotonic Agents/pharmacology , Cystathionine beta-Synthase/pharmacology , Cysteine/pharmacology , Hydrogen Sulfide/metabolism , Hydrogen-Ion Concentration/drug effects , Hydroxylamine/pharmacology , Lampreys/physiology , Oncorhynchus mykiss/physiology , Oxygen/metabolism
14.
Article in English | MEDLINE | ID: mdl-17500043

ABSTRACT

Potential humoral factors controlling an intestinal brake mechanism in Chinook salmon were characterised in terms of their effect on frequency and amplitude of spontaneous contractions in gastrointestinal (GI) rings. Concentration-response curves of gut contractility were produced for cholecystokinin-8 (CCK-8), gastrin-1, glucagon-like peptide-1 (GLP-1) and 5-hydroxytryptamine (5-HT) using gut rings from cardiac stomach (CS), pyloric stomach (PY), pyloric sphincter (Psp) and intestine (Int). Calculated log10 molar (M) EC50 values for CCK-8 (n=7) were: CS -8.15+/-0.90, PY -7.88+/-0.48, Psp -8.98+/-0.68, Int -8.93+/-0.64. Log10 M EC50 values calculated for gastrin 1 (n=7) were: CS -12.45+/-0.66, PY -12.55+/-0.63, Psp -9.35+/-0.78, Int -12.69+/-1.12. Log10 M EC50 values calculated for 5-HT (n=6) were: CS -4.78+/-1.05 and Psp -6.18+/-1.14. GLP -1 (n=4) produced no response in any of the tissues examined. Spontaneous contractions, measured as spikes per minute and the peak force generated were also measured for each hormone-tissue combination. The Psp generated the greatest mass-specific force, with stomach rings generating the least force. Dilutions of serum from fish diagnosed with gastric dilation air sacculitis (GDAS +ve) increased gut contractility compared to controls (GDAS -ve).


Subject(s)
Gastrointestinal Agents/pharmacology , Gastrointestinal Motility/drug effects , Glucagon-Like Peptide 1/pharmacology , Serotonin/pharmacology , Sincalide/pharmacology , Animals , Cardia/drug effects , Cardia/physiology , Dose-Response Relationship, Drug , Gastrointestinal Motility/physiology , In Vitro Techniques , Intestine, Small/drug effects , Intestine, Small/physiology , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Pylorus/drug effects , Pylorus/physiology , Salmon
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