Positive vs. negative inotropic effects of carbachol in avian atrial muscle: role of Ni-like protein.
Treatment with pertussis toxin not only prevents inhibitory effects (e.g., reduced adenylate cyclase activity, decreased voltage-dependent Ca2+ entry, increased K+ efflux, and negative inotropy) but also unmasks stimulant effects (e.g., membrane depolarization and positive inotropy) of carbachol in chick atria. Pertussis toxin prevents transducer proteins (Ni and No) from linking muscarinic receptors to either adenylate cyclase and Ca2+ channels or K+ channels. However, pertussis toxin treatment does not block N proteins linking the muscarinic receptor to stimulant membrane effects. Membrane depolarization by carbachol, attributed by others to increased Na+ entry, may stimulate Na-Ca exchange and positive inotropy, perhaps by activation of phospholipase D. Alternatively, carbachol could increase inositol triphosphate content and thereby release Ca2+ from the sarcoplasmic reticulum to increase the force of contraction. The ability of carbachol to increase phosphoinositide hydrolysis is resistant to pertussis toxin. The second-messenger role of phospholipid metabolites provides a foundation for testing the hypothesis that such metabolites are eventually involved in the stimulant actions of carbachol seen in pertussis toxin-treated preparations.
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002645:Chickens; D019204:GTP-Binding Proteins / Q000502:physiology*; D006325:Heart Atria; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins