THE DWINDLING SECRETORY RESPONSE OF THE PERFUSED ADRENAL MEDULLA OF THE CAT TO REPEATED INJECTIONS OF HISTAMINE

¹ Department of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia

The secretory response of the isolated perfused adrenal gland of the cat decreases rapidly upon the repeated injection of histamine at 10-minute intervals. By approximately the fifth injection, the response has fallen to about one-third of the initial response. Little further drop occurs as the injection of histamine is continued. A period of 45 minutes' rest after the ninth injection results in a significant increase in the secretion of catecholamines by a subsequent injection of histamine. Perfusion of the gland with medium containing dopa or dopamine significantly retards the rate of decline of secretory response to histamine. Dopamine did not, however, retard the rate of decline of the response in the presence of a dopamine--oxidase inhibitor. There is depletion of the catecholamine stores of the stimulated gland with complete recovery of the catecholamines in the perfusate. These results suggest that the dwindling response of the perfused adrenal medulla to histamine is due to depletion of the "readily secretable" store of catecholamine in the face of failure of the chromaffin cell to carry on adequate synthesis under these conditions. The maintenance of a nearly steady rate of secretion after the maximum decline in the response and the recovery of the response after a period of rest are possibly due to mobilization of catecholamines from within the chromaffin cell.