Inhibition of evoked acetylcholine release: two different mechanisms in the Torpedo electric organ.
The action of agents inhibiting evoked transmitter release was investigated by analysing the Ca2+ secretion relationship, electrophysiologically and biochemically, and by measuring the stimulation-induced 45Ca accumulation in the tissue. Transmitter release saturated at external Ca2+ concentrations higher than 4 mM, the releasing mechanism probably being the limiting step. Antagonists of Ca2+ entry (Mg2+, Cd2+, diltiazem) decreased the sensitivity of acetylcholine release to Ca2+, acting as competitive inhibitors, and reduced the stimulation-induced 45Ca accumulation. Quinacrine produced similar effects, indicating that it interacts primarily with Ca2+ entry. In contrast, oxotremorine and adenosine depressed transmitter release proportionally at all Ca2+ concentrations, acting as non-competitive inhibitors, and did not modify the stimulation-induced 45Ca accumulation. Their inhibitory effects were additive and reflected a decrease in the quantal content of the responses evoked. It is concluded that both drugs inhibit cholinergic transmission in the electric organ without altering Ca2+ entry into the nerve endings.
D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004557:Electric Organ / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D014101:Torpedo
D002121:Calcium Channel Blockers; D007473:Ion Channels; D010095:Oxotremorine; D011796:Quinacrine; D008274:Magnesium; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium