Molecular Pharmacology, Vol 7, 87-96, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Stimulation on the Levels of Tyrosine Hydroxylase, Dopamine -Hydroxylase, and Catecholamines in Intact and Denervated Rat Adrenal Glands

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

Rats were treated with insulin (5 international units/kg) alone and in combination with actinomycin D (1 mg/kg) to determine the effects of neural stimulation and the requirement for protein synthesis upon rat adrenal tyrosine hydroxylase, dopamine -hydroxylase (EC 1.14.2.1), and catecholamine levels. Four hours after insulin administration, the catecholamine levels were 80% depleted and required 4 days to recover to the control values. Dopamine -hydroxylase activity was decreased at 24 hr, recovered to control values at 48 hr, and increased above control levels at 96 hr. Tyrosine hydroxylase activity was unchanged at 4 hr, increased at 24 hr, and remained high for at least 96 hr. Treatment of rats with actinomycin D (1 mg/kg) 1 hr before insulin administration completely abolished the rise in tyrosine hydroxylase normally seen after 24 hr, even though appreciable depletion of catecholamines still occurred. Actinomycin D given 3 and 6 hr following treatment with insulin also blocked the rise in tyrosine hydroxylase activity observed at 24 hr, but if actinomycin D administration was delayed until 12 hr after insulin injection the rise in tyrosine hydroxylase activity was no longer blocked.

In rats with the nerve supply to the left adrenal gland cut, only the intact right gland responded to insulin, with a loss of catecholamines at 4 hr and an increase in tyrosine hydroxylase at 24 hr. Rats treated with acetylcholine (20 mg/kg) and eserine (0.1 mg/kg) showed increases in tyrosine hydroxylase activity not only in the intact right gland but also in the denervated left gland. These observations indicate that an intact nervous supply is not absolutely required to bring about a rise in tyrosine hydroxylase activity, and that exposure to the neurotransmitter itself (in this case acetylcholine) is sufficient. Whether acetylcholine is directly involved in the increased levels of tyrosine hydroxylase, or whether a secretory response by the gland is the essential link, has yet to be determined.

Rats that received actinomycin D (0.5 mg/kg) 1 hr before insulin showed no rise in tyrosine hydroxylase at 24 hr, but at 48 hr the enzyme activity was twice that of the controls. In rats with the left gland denervated, only the intact right gland had an increase in tyrosine hydroxylase 48 hr after treatment with acetylcholine and actinomycin D. The evidence suggests that this rise in tyrosine hydroxylase resulted from additional neural stimulation of the gland secondary to the physiological stress produced by actinomycin D, rather than from the expression of a long-lived signal.

Note:
ACKNOWLEDGMENTS We wish to thank Mrs. Nannie Jordan and Mrs. Dorothy Leathers for their skillful technical assistance.

This article has been cited by other articles:

				J. A. Herlein, D. A. Morgan, B. G. Phillips, W. G. Haynes, and W. I. Sivitz Antecedent Hypoglycemia, Catecholamine Depletion, and Subsequent Sympathetic Neural Responses Endocrinology, June 1, 2006; 147(6): 2781 - 2788. [Abstract] [Full Text] [PDF]

				C. Desnos, M.-P. Laran, K. Langley, D. Aunis, and J.-P. Henry Long Term Stimulation Changes the Vesicular Monoamine Transporter Content of Chromaffin Granules J. Biol. Chem., July 7, 1995; 270(27): 16030 - 16038. [Abstract] [Full Text] [PDF]

				T Yamaguchi, T Nagatsu, T Sugimoto, S Matsuura, T Kondo, R Iizuka, and H Narabayashi Effects of tyrosine administration on serum biopterin in normal controls and patients with Parkinson's disease Science, January 7, 1983; 219(4580): 75 - 77. [Abstract] [PDF]

				A. M. Goldberg and B. L. Welch Adaptation of the Adrenal Medulla: Sustained Increase in Choline Acetyltransferase by Psychosocial Stimulation Science, October 20, 1972; 178(4058): 319 - 320. [Abstract] [PDF]