EFFECT OF HEMICHOLINIUM ON THE CATECHOLAMINE DEPLETING ACTIONS OF RESERPINE, MORPHINE AND INSULIN IN RABBIT TISSUES

¹ Department of Pharmacology, College of Medical Sciences, University of Minnesota, Minneapolis, Minnesota

Studies were performed to determine whether or not acetylcholine is required for the neurally mediated catecholamine depleting actions of reserpine, morphine, and insulin on the adrenal medulla. Also, the possible involvement of acetylcholine in mediating the effects of these three drugs on catecholamine levels in the heart and brain stem was examined.

Rabbits, whose left splanchnic nerves had been severed 2 hours previously, were given reserpine (4 mg/kg, i.v.), morphine sulfate (150 mg/kg, s.c.) or insulin (2U/kg, s.c.) and killed 5 hours later. Another group of animals similarly treated also received hemicholinium no. 3 (HC-3), a compound known to inhibit the formation of acetylcholine, 1 hour prior to the administration of the depleting drugs. HC-3 was given in divided doses i.v. and s.c. (200 µg/kg total). Pretreatment with HC-3 failed to decrease the depletion of brain stem catecholamines caused by either reserpine, morphine or insulin. Neither morphine nor insulin reduced the concentration of catecholamines in the heart and the depleting effect of reserpine was not prevented by prior administration of HC-3. However, denervation or HC-3 pretreatment markedly impaired the catecholamine depleting effects of all three drugs on the adrenal medulla and administration of choline chloride prevented this impairment. None of the drugs reduced the catecholamine content of the denervated gland.

From these studies it appears that reserpine, in a dose of 4 mg/kg, acts directly on the heart and brain stem of the rabbit to reduce the concentration of catecholamines in these tissues, whereas the depleting effect on the adrenal medulla is indirectly exerted through an action on the central nervous system. The capacity of HC-3 to impair release of amines from the adrenal gland by reserpine, morphine or insulin, and its reversal by choline, indicate the participation of acetylcholine in the adreno medullary depletion induced by these drugs.