Receptor desensitization and the transient nature of the secretory response of adrenal chromaffin cells.
Transition of the cellular responsiveness to a cholinergic stimulation during a prolonged stimulation with acetylcholine (ACh) of adrenal chromaffin cells was studied by directly monitoring the secretory process in cell bed perfusion experiments. A pulsatile injection of hexamethonium during the prolonged stimulation caused an interruption of the response. Step-up of the ACh concentration in the declining phase of the primary response evoked an additional response. The magnitude of the response to the step-up was reduced by extracellular Ca2+ in a dose-dependent manner. However, neither the peak amplitude nor the declining rate of the primary response was affected by Ca2+ in such a direction. These results suggest that the transient nature of the ACh-evoked response is mainly attributable to the inactivation of transduction mechanisms between receptor stimulation and channel activation. Although Ca2+-facilitated desensitization of nicotinic receptors is in process during the stimulation, such a desensitization may account only insignificantly for the transient nature.
D000109:Acetylcholine / Q000494:pharmacology*; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D006584:Hexamethonium Compounds; D007473:Ion Channels; D011950:Receptors, Cholinergic; D018738:Hexamethonium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium