Interaction between prostanoids, NO, and VIP in modulation of duodenal alkaline secretion and motility

1996 ◽  
Vol 271 (4) ◽  
pp. G582-G590 ◽  
Author(s):  
M. Sababi ◽  
A. Hallgren ◽  
O. Nylander
Keyword(s):  
Smooth Muscle ◽  
Methyl Ester ◽  
Inhibitory Action ◽  
Muscle Relaxation ◽  
Intraluminal Pressure ◽  
Smooth Muscle Relaxation ◽  
Pressure Measurements ◽  
Stimulatory Action ◽  
Duodenal Motility ◽  
Alkaline Secretion

The relation between duodenal motility and duodenal mucosal alkaline secretion (DMAS) was examined in anesthetized rats. The duodenum was perfused with saline, and DMAS was determined by titration. Duodenal motility, assessed by intraluminal pressure measurements, was induced by indomethacin and/or N omega-nitro-L-arginine methyl ester (L-NAME) and inhibited by iloprost or vasoactive intestinal peptide (VIP). Six of 66 rats showed spontaneous duodenal contractions. Basal DMAS was higher in these rats than in those without contractions. Rats treated with indomethacin and L-NAME before abdominal operation exhibited duodenal motility postoperatively and had higher DMAS than in controls. Iloprost abolished both the duodenal motility increase and increase in DMAS induced by indomethacin. L-NAME-induced motility and increase in DMAS were antagonized by L-arginine. VIP increased DMAS without affecting motility. VIP abolished indomethacin-induced motility and augmented indomethacin-stimulated DMAS. VIP reduced L-NAME-induced motility and slightly increased L-NAME-stimulated DMAS. It is concluded that DMAS varies with duodenal motility. Prostaglandins and NO inhibit duodenal motility, thereby indirectly reducing DMAS. VIP may have dual effects on DMAS, an inhibitory action mediated via smooth muscle relaxation and a stimulatory action independent of motility.

Mechanism of internal anal sphincter smooth muscle relaxation by phorbol 12,13-dibutyrate

2001 ◽  
Vol 280 (6) ◽  
pp. G1341-G1350 ◽  
Author(s):  
Sushanta Chakder ◽  
D. N. K. Sarma ◽  
Satish Rattan
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Inhibitory Action ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Muscle Cells ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Tone

We investigated the mechanism of the inhibitory action of phorbol 12,13-dibutyrate (PDBu), one of the typical protein kinase C (PKC) activators, in in vitro smooth muscle strips and in isolated smooth muscle cells of the opossum internal anal sphincter (IAS). The inhibitory action of PDBu on IAS smooth muscle (observed in the presence of guanethidine + atropine) was partly attenuated by tetrodotoxin, suggesting that a part of the inhibitory action of PDBu is via the nonadrenergic, noncholinergic neurons. A major part of the action of PDBu in IAS smooth muscle was, however, via its direct action at the smooth muscle cells, accompanied by a decrease in free intracellular Ca2+ concentration ([Ca2+]i) and inhibition of PKC translocation. PDBu-induced IAS smooth muscle relaxation was unaffected by agents that block Ca2+ mobilization and Na+-K+-ATPase. The PDBu-induced fall in basal IAS smooth muscle tone and [Ca2+]i resembled that induced by the Ca2+ channel blocker nifedipine and were reversed specifically by the Ca2+ channel activator BAY K 8644. We speculate that a major component of the relaxant action of PDBu in IAS smooth muscle is caused by the inhibition of Ca2+ influx and of PKC translocation to the membrane. The specific role of PKC downregulation and other factors in the phorbol ester-mediated fall in basal IAS smooth muscle tone remain to be determined.

Mechanism of action of cholera toxin on the opossum internal anal sphincter smooth muscle

1999 ◽  
Vol 277 (1) ◽  
pp. G152-G160 ◽  
Author(s):  
Ya-Ping Fan ◽  
Sushanta Chakder ◽  
Satish Rattan
Keyword(s):  
Smooth Muscle ◽  
Cholera Toxin ◽  
Anal Sphincter ◽  
Mechanism Of Action ◽  
Internal Anal Sphincter ◽  
Inhibitory Action ◽  
Kinase Inhibitor ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Basal Tone

Cholera toxin (CTX), an activator of Gsprotein, is an important pharmacological tool in G protein research. The effect and the mechanism of action of CTX in the gastrointestinal smooth muscle, including the internal anal sphincter (IAS), are not known. The present investigation was carried out to examine the effects of CTX on the signal transduction associated with the adenylate cyclase (AC) pathway on the basal tone of the IAS smooth muscle. CTX caused a prompt and dose-dependent fall in the basal tone of the IAS that was not affected by the neurotoxins TTX and ω-conotoxin or the nitric oxide synthase inhibitor NG-nitro-l-arginine. The cyclooxygenase inhibitor indomethacin, cAMP-dependent protein kinase inhibitor Rp-8-bromoadenosine 3′,5′ cyclic monophosphorothioate inhibited CTX-induced IAS smooth muscle relaxation. Furthermore, CTX caused a concentration-dependent relaxation of the isolated smooth muscle cells (SMC) of the IAS, which was blocked by Gsα antibody (Gsα-Ab). The IAS smooth muscle relaxation was accompanied with an increase in the GTPase activity that was also specifically blocked by Gsα-Ab. We conclude that a major part of the inhibitory action of CTX in the IAS is via the direct response of the SMC that is linked with Gsprotein to the AC pathway. A part of the inhibitory action of CTX on the smooth muscle occurs via the activation of cyclooxygenase pathway. The relative contribution of such actions of CTX in the smooth muscle in the gastrointestinal motility disturbances following cholera infection remains to be determined.

Mechanism of inhibition of VIP-induced LES relaxation by heme oxygenase inhibitor zinc protoporphyrin IX

1999 ◽  
Vol 276 (1) ◽  
pp. G138-G145 ◽  
Author(s):  
Satish Rattan ◽  
Ya-Ping Fan ◽  
Sushanta Chakder
Keyword(s):  
Smooth Muscle ◽  
G Protein ◽  
Heme Oxygenase ◽  
Inhibitory Action ◽  
Muscle Relaxation ◽  
Protoporphyrin Ix ◽  
Significant Inhibition ◽  
Smooth Muscle Relaxation ◽  
Zinc Protoporphyrin ◽  
Protein Activation

The putative heme oxygenase inhibitor zinc protoporphyrin IX (ZnPP IX) is known to exert diverse actions, including inhibitory action on smooth muscle relaxation by vasoactive intestinal polypeptide (VIP). The studies were performed in the opossum lower esophageal sphincter (LES) smooth muscle to determine the site of the inhibitory action of ZnPP IX in the smooth muscle relaxation by VIP. We also examined the effect of a direct Gs protein activator, cholera toxin (CTX), known to stimulate adenylate cyclase (AC). CTX caused relaxation of the LES smooth muscle by its action directly at the smooth muscle cells. The convergence of the common mechanisms of actions of VIP and CTX on AC was determined by the suppression of their effects by the AC inhibitor and CTX desensitization. ZnPP IX caused attenuation of the LES smooth muscle relaxation by VIP but not by CTX. ZnPP IX but not zinc deuteroporphyrin IX caused significant inhibition of VIP binding to the membrane receptor. We conclude that ZnPP IX attenuates VIP-induced LES smooth muscle relaxation by inhibition of VIP binding to G protein-coupled receptors linked to AC at a point proximal to G protein activation.

scholarly journals A.122 Vascular effects of propofol: smooth muscle relaxation in human isolated veins and arteries

1996 ◽  
Vol 76 ◽  
pp. 38-39
Author(s):  
Eric Le Pelley ◽  
Pierre Corbi ◽  
Thierry Chataigneau ◽  
Robert Tricoche ◽  
Jacques Fusciardi
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Vascular Effects

216Acute administration of estradiol induces bladder smooth muscle relaxation through non-genomic pathways

2005 ◽  
Vol 4 (3) ◽  
pp. 56
Author(s):  
M. Dambros ◽  
P. Palma ◽  
C. Riccetto ◽  
R. Fraga ◽  
M. Thiel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Bladder Smooth Muscle

Role of cGMP in relaxation of vascular and other smooth muscle

1989 ◽  
Vol 67 (4) ◽  
pp. 251-262 ◽  
Author(s):  
Kanji Nakatsu ◽  
Jack Diamond
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitors ◽  
Current Evidence ◽  
Smooth Muscle Relaxation ◽  
Drug Induced ◽  
Intracellular Cgmp ◽  
Tissue Content

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.

scholarly journals Arteriolar vasodilation involves actin depolymerization

2018 ◽  
Vol 315 (2) ◽  
pp. H423-H428
Author(s):  
Philip S. Clifford ◽  
Brian S. Ferguson ◽  
Jeffrey L. Jasperse ◽  
Michael A. Hill
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Smooth Muscle Relaxation ◽  
Myosin Light Chain Phosphorylation ◽  
Actin Depolymerization

It is generally assumed that relaxation of arteriolar vascular smooth muscle occurs through hyperpolarization of the cell membrane, reduction in intracellular Ca2+ concentration, and activation of myosin light chain phosphatase/inactivation of myosin light chain kinase. We hypothesized that vasodilation is related to depolymerization of F-actin. Cremaster muscles were dissected in rats under pentobarbital sodium anesthesia (50 mg/kg). First-order arterioles were dissected, cannulated on glass micropipettes, pressurized, and warmed to 34°C. Internal diameter was monitored with an electronic video caliper. The concentration of G-actin was determined in flash-frozen intact segments of arterioles by ultracentrifugation and Western blot analyses. Arterioles dilated by ~40% of initial diameter in response to pinacidil (1 × 10−6 mM) and sodium nitroprusside (5 × 10−5 mM). The G-actin-to-smooth muscle 22α ratio was 0.67 ± 0.09 in arterioles with myogenic tone and increased significantly to 1.32 ± 0.34 ( P < 0.01) when arterioles were dilated with pinacidil and 1.14 ± 0.18 ( P < 0.01) with sodium nitroprusside, indicating actin depolymerization. Compared with control vessels (49 ± 5%), the percentage of phosphorylated myosin light chain was significantly reduced by pinacidil (24 ± 2%, P < 0.01) but not sodium nitroprusside (42 ± 4%). These findings suggest that actin depolymerization is an important mechanism for vasodilation of resistance arterioles to external agonists. Furthermore, pinacidil produces smooth muscle relaxation via both decreases in myosin light chain phosphorylation and actin depolymerization, whereas sodium nitroprusside produces smooth muscle relaxation primarily via actin depolymerization. NEW & NOTEWORTHY This article adds to the accumulating evidence on the contribution of the actin cytoskeleton to the regulation of vascular smooth muscle tone in resistance arterioles. Actin depolymerization appears to be an important mechanism for vasodilation of resistance arterioles to pharmacological agonists. Dilation to the K+ channel opener pinacidil is produced by decreases in myosin light chain phosphorylation and actin depolymerization, whereas dilation to the nitric oxide donor sodium nitroprusside occurs primarily via actin depolymerization. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/vascular-smooth-muscle-actin-depolymerization/ .

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