{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:59:50Z","timestamp":1789621190391,"version":"build-2803163510"},"reference-count":0,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[1993,10,1]]},"abstract":"<jats:p> Vasoactive intestinal peptide (VIP) and peptide histidine-isoleucine (PHI) receptors and the signaling pathways to which they are coupled were characterized in dispersed gastric smooth muscle cells. Radioligand binding using 125I-labeled VIP and PHI identified 4 classes of receptors: VIP-preferring and PHI-preferring receptors recognized by both ligands and readily desensitized by the preferred ligand, and VIP-specific and PHI-specific receptors recognized by only 1 ligand and resistant to desensitization. All except VIP-specific receptors were coupled to adenylate cyclase. VIP-specific receptors mediated a G protein-coupled Ca2+ influx that led to activation of NO synthase (NOS), NO-dependent activation of soluble guanylate cyclase, and activation of guanosine 3',5'-cyclic monophosphate (cGMP) kinase resulting in muscle relaxation. The entire cascade was blocked by Ca2+ channel and\/or calmodulin antagonists. The NOS inhibitor NG-nitro-L-arginine abolished L-[3H]citrulline (coproduct of NO synthesis) and cGMP generation and partly inhibited (52 +\/- 4%) relaxation. The components of response mediated by VIP-specific receptors (increase in [Ca2+]i, L-[3H]citrulline, and cGMP) were preserved after desensitization. Insertion of guanosine 5'-O-(beta-thio)diphosphate into reversibly permeabilized muscle cells abolished responses mediated by VIP-preferring and VIP-specific receptors. VIP stimulated both adenosine 3',5'-cyclic monophosphate (cAMP)-kinase and cGMP-kinase activities consistent with stimulation of cAMP and cGMP. Both kinases contributed to relaxation that was partly inhibited by cAMP-kinase [H-89 and (R)-p-adenosine 3',5'-cyclic monophosphorothioate] and cGMP-kinase (KT-5823) inhibitors and abolished by a combination of the 2 types of inhibitors. We conclude that VIP-specific receptors mediate a G protein-coupled Ca2+ influx leading to activation of a constitutive Ca2+\/calmodulin-dependent NOS and generation of NO, which is partly responsible for relaxation in smooth muscle. <\/jats:p>","DOI":"10.1152\/ajpgi.1993.265.4.g660","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T00:00:23Z","timestamp":1514073623000},"page":"G660-G671","source":"Crossref","is-referenced-by-count":10,"title":["VIP-mediated G protein-coupled Ca2+ influx activates a constitutive NOS in dispersed gastric muscle cells"],"prefix":"10.1152","volume":"265","author":[{"given":"K. S.","family":"Murthy","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Virginia, Richmond 23298."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Virginia, Richmond 23298."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Virginia, Richmond 23298."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. R.","family":"Grider","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Virginia, Richmond 23298."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. M.","family":"Makhlouf","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Virginia, Richmond 23298."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.1993.265.4.G660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T19:02:18Z","timestamp":1567969338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.1993.265.4.G660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1993,10,1]]}},"alternative-id":["10.1152\/ajpgi.1993.265.4.G660"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.1993.265.4.g660","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,10,1]]}}}