Signaling via histamine receptors in cat duodenal smooth muscle cells.
Histamine produced concentration-dependent contractions in cat duodenal smooth muscle cells that were obtained by enzymatic digestion of smooth muscle with collagenase F. Pyrilamine, an H1 receptor antagonist, inhibited the contractile response while famotidine, an H2 receptor antagonist, augmented it. In cells with selectively preserved H1 receptors, produced by pretreatment with pyrilamine followed by inactivation of all unprotected receptors with N-ethylmaleimide, histamine-induced contraction was significantly augmented as compared with control cells. Pertussis toxin (PTX) had no effect on contraction, suggesting that the H1 receptor is coupled to a PTX-insensitive G protein. Gi2, Gi3, Go, Gs, and Gq subunits were present in cat duodenum, and histamine-induced contraction was inhibited by Gq antibody after cell permeabilization. Neomycin, a PLC inhibitor, inhibited the histamine-induced cell contraction, but not rhoCMB, a PLD inhibitor, or DEDA, a PLA2 inhibitor. Heparin, an IP3 receptor inhibitor, inhibited contraction whereas chelerythrine, a PKC inhibitor, had no effect. We conclude that histamine-induced contraction in cat duodenal smooth muscle cells is mediated by H1 receptors coupled to a PTX-insensitive Gq protein and results in activation of phosphatidylinositol-specific phospholipase C (PI-PLC).
Jeong
Ji Hoon
JH
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Yun
Mun Chul
MC
Shin
Chang Yell
CY
Lee
Tai Sang
TS
Song
Hyun Ju
HJ
Sohn
Uy Dong
UD
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002415:Cats; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006632:Histamine / Q000031:analogs & derivatives / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010617:Phenanthridines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D015738:Famotidine; D006632:Histamine; D006493:Heparin; C016299:chelerythrine; D037342:Pertussis Toxin; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011738:Pyrilamine; D005033:Ethylmaleimide