Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relaxant effect of capsaicin (300 nM) has been studied on mucosa-free circular strips of the human sigmoid colon in vitro. The response of precontracted preparations to capsaicin (sub-maximal relaxation) was reduced by over 50% by the nitric oxide synthase inhibitor N(G)-nitro- L-arginine (L-NOARG; 20 microM or 100 microM) or by the guanylate cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), but not by tetrodotoxin (1 microM) or the P(2) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS; 50 microM). L-NOARG or ODQ caused moderate contraction of the circular muscle, indicating a tonic "nitrergic" control. Anandamide (1-100 microM), an endogenous cannabinoid and capsaicin VR(1) receptor stimulant, failed to either mimic or modify the response to capsaicin (300 nM). It is proposed that capsaicin causes the release of smooth muscle relaxant substance(s) from afferent nerve endings in the gut wall, in a tetrodotoxin-resistant manner. Nitric oxide (possibly released from capsaicin-sensitive afferents) plays an important role in the capsaicin-evoked response. No evidence has been found for an involvement of PPADS-sensitive P(2) purinoceptors in the response to capsaicin or for a stimulation or inhibition of capsaicin-sensitive receptors by anandamide in the human sigmoid colon.
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PMID:Nitric oxide is involved in the relaxant effect of capsaicin in the human sigmoid colon circular muscle. 1238 81

The transmitters involved in the non-nitrergic component of the non-adrenergic, non-cholinergic (NANC) inhibitory response of the rat small intestinal longitudinal muscle to electrical field stimulation of its nerves is a matter of controversy. The present study is the first one to utilise a combination of a nitric oxide synthase inhibitor and a P(2) purinoceptor antagonist for studying this response. We found that the P(2) purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-5) M) abolished the non-nitrergic NANC relaxation to electrical field stimulation (10 Hz). PPADS alone provided a significant, moderate inhibitory action. PPADS specifically inhibited relaxations due to exogenous adenosine 5'-triphosphate (ATP) or alpha,beta-methylene ATP. The guanylate cyclase blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10(-6) M) did not add to the inhibitory action of N(G)-nitro-L-arginine on field stimulation-induced relaxation. ODQ abolished the relaxant effect of the nitric oxide donors nitroglycerin or sodium nitroprusside. These data indicate that: (1) nitric oxide and ATP fully account for the field stimulation-induced relaxation in the rat ileal strip under the experimental conditions of this study, and (2) no ODQ-sensitive guanylate cyclase-mediated mechanism is involved in the non-nitrergic component of the NANC relaxation.
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PMID:P(2) purinoceptors account for the non-nitrergic NANC relaxation in the rat ileum. 1672 56

The present study was designed to characterize the urinary bladder-derived relaxant factor that was demonstrated by acetylcholine-induced relaxation response in a coaxial bioassay system consisting of rat bladder as the donor organ and rat anococcygeus muscle as the assay tissue. The concentration-dependent relaxation to acetylcholine (10 nM-1 mM) was inhibited by atropine but was not altered by the antagonists of calcitonin gene-related peptide (CGRP 8-37), vasoactive intestinal peptide (VIP 6-28), tachykinin NK1 (L-732138), tachykinin NK2 (MEN-10376), tachykinin NK3 (SB-218795), purinergic P2 (PPADS) and adenosine (CGS 15943) receptors as well as alpha-chymotrypsin. Adenylate cyclase inhibitor SQ-22536 and protein kinase A inhibitor KT-5720 significantly inhibited the acetylcholine response while guanylate cyclase inhibitor ODQ, and protein kinase C inhibitor H-7 did not have any effect. The P2X agonist alpha,beta-methylene ATP (10 nM-0.1 mM) also produced concentration-dependent relaxation response that was inhibited by PPADS, SQ-22536 and KT-5720 in the coaxial bioassay system. In bladder strips, acetylcholine and alpha,beta-methylene ATP elicited concentration-dependent contractions that were not altered in the presence of SQ-22536 and KT-5720. In conclusion, the urinary bladder-derived relaxant factor that was recognized by the coaxial bioassay system is neither a peptide of the bladder neurons nor a purinergic mediator but adenylate cyclase and protein kinase A are involved in its release and/or relaxant effect. Furthermore, activation of purinergic P2X receptors besides the muscarinic receptors leads to the release of this factor.
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PMID:Rat urinary bladder-derived relaxant factor: studies on its nature and release by coaxial bioassay system. 1862 Oct 43