Molecular Pharmacology, Vol 7, 389-396, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Acetylcholine-Induced Stimulation of Catecholamine Recovery in Denervated Rat Adrenals after Reserpine-Induced Depletion

¹ Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27706

The present studies evaluate neurogenic factors affecting the rate of catecholamine recovery following depletion in the rat adrenal medulla. Rats with their left adrenal glands denervated received reserpine, 2.5 mg/kg intraperitoneally, daily for 3 consecutive days. The catecholamine contents of the denervated glands were lowered by 54%, and those of the intact glands, by 80%. Four days after the last injection of reserpine the intact glands had recovered their normal catecholamine content, but the denervated glands were still significantly depleted.

Rats treated with reserpine and with repeated intravenous injections of acetylcholine 1 day after the last reserpine injection completely recovered their catecholamine levels 4 days after the last injection of reserpine, in both intact and denervated glands.

The denervated glands showed no increase in tyrosine hydroxylase activity after reserpine treatment, while the enzyme levels of the intact glands rose to 350% of controls. Treatment with acetylcholine increased the tyrosine hydroxylase activity in denervated glands to 180-265% of controls, and that of intact glands to 550-600% of control values.

Dopamine -hydroxylase activity was increased by 70% in denervated glands following reserpine treatment, while in the intact glands it increased by 160%. In contrast to its effect on tyrosine hydroxylase activity, acetylcholine had no effect on dopamine -hydroxylase activity in denervated glands of animals examined 2 days after completion of reserpine treatment, and it caused only a 25% increase in the enzyme activity of animals 4 days after reserpine administration.

The data show that the delay in recovery of catecholamine content observed after reserpine treatment in denervated rat adrenals can be overcome by exposing the gland to its normal secretagogue, acetylcholine.

Note:
ACKNOWLEDGMENTS The authors wish to thank Mrs. Nannie Jordan and Mrs. Dorothy Leathers for their excellent technical assistance.