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)

(1) The aim of the present study was to verify a possible involvement of nitric oxide (NO) and of tachykinins in the contractile and relaxant effects caused by the activation of protease-activated receptor (PAR)-1 and PAR-2 in the longitudinal muscle of rat colon. (2) Mechanical responses to the PAR-1 activating peptides, SFLLRN-NH(2) (10 nM-10 micro M) and TFLLR-NH(2) (10 nM-10 micro M), and to the PAR-2-activating peptide, SLIGRL-NH(2) (10 nM-10 micro M), were examined in vitro in the absence and in the presence of different antagonists. (3) The relaxation induced by SFLLRN-NH(2), TFLLR-NH(2) and SLIGRL-NH(2) was antagonised by the inhibitor of NO synthase L-N(omega)-nitroarginine methyl ester (300 micro M), or by the inhibitor of the guanylyl cyclase, 1-H-oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one (10 micro M). (4) The contractile responses to PAR-1 and PAR-2 activation were concentration-dependently attenuated by SR140333 (0.1-1 micro M), NK(1) receptor antagonist, or by SR48968 (0.1-1 micro M), NK(2) receptor antagonist. The combined pretreatment with SR140333 (1 micro M) and SR48968 (1 micro M) produced additive suppressive effects on the contractile responses to PAR activation. Pretreatment of the preparation with capsaicin (10 micro M) markedly reduced the contractions evoked by SFLLRN-NH(2), TFLLR-NH(2) and SLIGRL-NH(2), while omega-conotoxin GVIA (0.2 micro M) had no effect. (5) The present results suggest that in rat colonic longitudinal muscle, PAR-1 and PAR-2 activation can evoke (i) relaxation through the production of NO or (ii) contraction through the release of tachykinins, likely, from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.
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PMID:Involvement of nitric oxide and tachykinins in the effects induced by protease-activated receptors in rat colon longitudinal muscle. 1278 19

Endothelium-dependent vasodilation via protease-activated receptor 2 (PAR2) is preserved in mesenteric arteries from SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome even though nitric oxide (NO)-mediated vasodilation is attenuated. Therefore, we examined the PAR2 mechanisms underlying metabolic syndrome-resistant vasodilation in SHRSP.ZF aortas with ageing. In isolated aortas, the PAR2 agonist 2-furoyl-LIGRLO-amide (2fly) caused vasodilation that was sustained in male SHRSP.ZF until 18 weeks of age, but was attenuated afterwards compared with age-matched Wistar-Kyoto rats (controls) at 23 weeks. In contrast, acetylcholine-induced vasodilation was impaired in SHRSP.ZF already at 18 weeks of age. Treatments of aortas with inhibitors of NO synthase and soluble guanylate cyclase abolished the sustained 2fly- and residual acetylcholine-induced vasodilation in SHRSP.ZF at 18 weeks of age. In the aortas of SHRSP.ZF, 8-bromo-cGMP-induced vasodilation, NO production and cGMP accumulation elicited by 2fly were not different from in the controls. PAR2 agonist increased phospho-Ser1177-eNOS protein content only in SHRSP.ZF aortas. These results indicate that vasodilation mediated by PAR2 is sustained even though NO-dependent relaxation is attenuated with ageing/exposure to metabolic disorders in large-caliber arteries from SHRSP.ZF. PAR2 stimulation of NO production via an additional pathway that targets phosphorylation of Ser1177-eNOS suggests a regulatory mechanism for sustaining agonist-mediated vasodilation in metabolic syndrome.
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PMID:Enhanced Nitric Oxide Synthase Activation via Protease-Activated Receptor 2 Is Involved in the Preserved Vasodilation in Aortas from Metabolic Syndrome Rats. 2676 May 32