title: Muscarinic acetylcholine receptor compounds alter net Ca2+ flux and contractility in an invertebrate smooth muscle.
abstract: Responses of a holothurian smooth muscle to a range of muscarinic (M(1) to M(5)) acetylcholine receptor (mAChR) agonists and antagonists were surveyed using calcium (Ca(2+))-selective electrodes and a mechanical recording technique. Most of the mAChR agonists and antagonists tested increased both contractility and net Ca(2+) efflux, with M(1)-specific agents like oxotremorine M being the most potent in their action. To investigate the possible sources of Ca(2+) used during mAChR activation, agents that disrupt intracellular Ca(2+) ion sequestration [cyclopiazonic acid (CPA), caffeine, ryanodine], the phosphoinositide signaling pathway [lithium chloride (LiCl)], and L-type Ca(2+) channels (diltiazem and verapamil) were used to challenge contractions induced by oxotremorine M. These contractions were blocked by treatment with CPA, caffeine, LiCl, and by channel blockers, diltiazem and verapamil, but were unaltered by ryanodine. Our data suggest that this smooth muscle had an M(1,3,5)-like receptor that was associated with the phosphoinositide signaling pathway that relied on intracellular Ca(2+) stores, but secondarily used extracellular Ca(2+) via the opening of L-type channels.
authors.affiliation: Department of Biology, Abington College, Penn State University, Abington, PA 19001, USA. cld5@psu.edu
authors.forename: C Leah
authors.initials: CL
authors.lastname: Devlin
authors.forename: William
authors.initials: W
authors.lastname: Amole
authors.forename: Shawn
authors.initials: S
authors.lastname: Anderson
authors.forename: Kyle
authors.initials: K
authors.lastname: Shea
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004566:Electrodes; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007448:Invertebrates / Q000187:drug effects / Q000502:physiology; D018021:Lithium Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012616:Sea Cucumbers
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012433:Ryanodine; D002110:Caffeine; D018021:Lithium Chloride; D002118:Calcium