title: Inhibition of Na+,K+-ATPase by ouabain opens calcium channels coupled to acetylcholine release in guinea pig myenteric plexus.
abstract: Ouabain, an Na+K+ATPase inhibitor, increases the release of acetylcholine (ACh) from various preparations in a Ca2+ -independent way. However, in other preparations the release of ACh evoked by ouabain is dependent on the presence of extracellular calcium. In the present study, we have labeled the ACh of myenteric plexus longitudinal muscles of guinea pig ileum and compared the effect of calcium channel blockers on ouabain-evoked release of [3H]ACh. Release of [3H]ACh evoked by ouabain is dose dependent and decreased markedly in the absence of calcium or in the presence of cadmium, a nonspecific calcium channel blocker. N-type calcium channel blockage by the omega-conotoxins GVIA (selective N-type calcium channel blocker) and MVIC (a nonselective calcium channel blocker) inhibited by 45 and 55%, respectively, the release of [3H]ACh. L-type calcium channel suppression by low concentrations of verapamil, nifedipine, and diltiazem had no effect on the release of [3H]ACh. The release of transmitter was also not affected significantly by nickel, a T-type calcium channel blocker. In addition, omega-agatoxin-IVA, at concentrations that block P- and Q-type calcium channels, did not affect significantly the release of [3H]ACh. Thus, extracellular Ca2+ is essential for the release of ACh induced by ouabain from guinea pig ileum myenteric plexus. In this preparation, the N-type calcium channel plays a dominant role in transmitter release evoked by inhibition of Na+K+-ATPase, but other routes of calcium entry in addition to these channels can also support the release of neurotransmitter induced by ouabain.
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Minas Gerais, Brasil.
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
authors.forename: M V
authors.initials: MV
authors.lastname: Gomez
authors.forename: M A
authors.initials: MA
authors.lastname: Prado
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000201:enzymology / Q000294:innervation; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009132:Muscles / Q000201:enzymology / Q000648:ultrastructure; D009197:Myenteric Plexus / Q000201:enzymology* / Q000648:ultrastructure; D010042:Ouabain / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013111:Spider Venoms / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D008978:Mollusk Venoms; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D002104:Cadmium; D014316:Tritium; C075851:omega-conotoxin-MVIIC; D010042:Ouabain; D020866:omega-Conotoxin GVIA; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D002118:Calcium