Calcium-independent desensitization of rises in intracellular free Ca2+ concentration and catecholamine release in cultured adrenal chromaffin cells.
Exposure of adrenal chromaffin cells to carbamylcholine (CCh) in the absence of extracellular Ca2+ suppressed rises in intracellular free Ca2+ concentration ([Ca2+]i) induced by subsequent addition of Ca2+ into the incubation medium. The extent of the suppression was dependent on the concentration of CCh and the duration of exposure. A similar inhibitory effect of CCh was also observed in the case of catecholamine release. In contrast, pretreatment with 56 mM K+ did not affect these two responses induced by Ca2+. Recovery from the desensitized state was rapid, since the responses became normal within 3 min following washout of the maximum concentration of CCh. These results show that, in Ca2+-free medium, exposure of the cells to CCh induces desensitization as indicated by diminished rise in [Ca2+]i and reduced release of catecholamines. These phenomena were not due to direct inhibition of voltage-dependent Ca2+ channels by CCh, but seem to be due to an uncoupling of signal transduction between the nicotinic receptor and Ca2+ channel.
Sasakawa
N
N
Ishii
K
K
Kato
R
R
D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects
D002395:Catecholamines; D007473:Ion Channels; D011978:Receptors, Nicotinic; D002217:Carbachol; D011188:Potassium; D002118:Calcium