Summary
One pair of rat adrenals was found to contain 100–200 ng of dopamine (DA), the molar concentration ratio of DA to adrenaline + noradrenaline being about 0.005. After inhibition of tyrosine hydroxylase DA decreased exponentially, with a half life of 1.35 h. Insulin and the ganglionic blocking agent chlorisondamine caused within 90 min an increase in adrenal DA which was prevented by a high spinal transection. Chlorisondamine prevented the insulin-induced depletion of adrenaline but the rise in DA persisted. The insulin-induced increase in DA was enhanced by inhibitors of dopamine-β-hydroxylase and monoamine oxidase.
The data support the view that neurogenic stimulation of the adrenal medulla activates the rate-limiting synthetic enzyme tyrosine hydroxylase by a mechanism which can be dissociated from the secretory response. Therefore, reduced end-product inhibition does not seem to be a likely explanation of the increased tyrosine hydroxylase activity. The observations suggest that neurogenic short-term activation of tyrosine hydroxylase, like the long-term induction of this enzyme is mediated by special receptors, which can be distinguished from the nicotinic receptors mediating the secretory response.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Atack, C. V., Eriksson, L. E., Melander, A.: Intracellular distribution of amines and calcitonin in the sheep thyroid gland. J. Ultrastruct. Res. 41, 484–498 (1972).
Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single strong cation exchange column by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970).
Carlsson, A., Waldeck, B.: A fluorimetric method for the determination of dopamine (3-hydroxy-tyramine). Acta physiol. scand. 44, 293–298 (1958).
Dairman, W., Gordon, R., Spector, S., Sjoerdsma, A., Udenfriend, S.: Increased synthesis of catecholamines in the intact rat following administration of α-adrenergic blocking agent. Molec. Pharmacol. 4, 457–464 (1968).
D'Anzi, F. A.: Morphological and biochemical observations on the catecholamine-storing vesicles of rat adrenomedullary cells during insulin-induced hypoglycemia. Amer. J. Anat. 125, 381–398 (1969).
Eade, N. R.: The distribution of the catecholamines in homogenates of the bovine adrenal medulla. J. Physiol. (Lond.) 141, 183–192 (1958).
Gordon, R., Spector, S., Sjoerdsma, A., Udenfriend, S.: Increased synthesis of norepinephrine and epinephrine in the intact rat during exercise and exposure to cold. J. Pharmacol. exp. Ther. 153, 440–447 (1966).
Guidotti, A., Costa, E.: In vivo estimation of 3′,5′-adenosine monophosphate and catecholamine turnover rate in rat adrenal medulla after denervation and reserpine. In: Proceedings of the Fifth International Congress on Pharmacology, San Francisco (July 1972). Volunteer abstract 541.
Hökfelt, B.: Noradrenaline and adrenaline in mammalian tissues. Acta physiol. scand. 25, Suppl. 92 (1951).
Laduron, P.: N-methylation of dopamine to epinine in adrenal medulla: A new model for the biosynthesis of adrenaline. Arch. int. Pharmacodyn. 195, 197–208 (1972).
Lishajko, F.: Dopamine secretion from the isolated perfused sheep adrenal. Acta physiol. scand. 79, 405–410 (1970).
Mueller, R. A., Thoenen, A., Axelrod, J.: Inhibition of trans-synaptically increased tyrosine hydroxylase activity by cyclohexamide and actinomycin D. Molec. Pharmacol. 5, 463–469 (1969).
Mueller, R. A., Thoenen, H., Axelrod, J.: Inhibition of neuronally induced tyrosine hydroxylase by nicotinic receptor blockade. Europ. J. Pharmacol. 10, 51–56 (1970).
Patrick, R. L., Kirshner, N.: Effect of stimulation on the levels of tyrosine hydroxylase, dopamine beta-hydroxylase, and catecholamines in intact and denervated rat adrenal glands. Molec. Pharmacol. 7, 87–96 (1971a).
Patrick, R. L., Kirshner, N.: Acetylcholine-induced stimulation of catecholamine recovery in denervated rat adrenals after reserpine-induced depletion. Molec. Pharmacol. 7, 389–396 (1971b).
Sedvall, G. C., Kopin, I. J.: Influence of sympathetic denervation and nerve impulse activity of tyrosine hydroxylase in the rat submaxillary gland. Biochem. Pharmacol. 16, 39–46 (1967).
Stjärne, L.: The synthesis, uptake and storage of catecholamines in the adrenal medulla. In: H. Blaschko and E. Muscholl (eds.): Catecholamines. Handbook of Exp. Pharmacol. New Series XXXIII, pp. 231–269. Berlin-Heidelberg-New York: Springer 1972.
Svensson, T., Waldeck, B.: On the significance of central noradrenaline for motor activity: Experiments with a new dopamine beta-hydroxylase inhibitor. Europ. J. Pharmacol. 7, 278–282 (1969).
Udenfriend, S., Cooper, J. R., Clark, C. T., Baer, J. E.: Rate of turnover of epinephrine in the adrenal medulla. Med. Science 117, 663–665 (1953).
Weiner, N., Cloutier, G., Bjur, R., Pfeffer, R. I.: Modification of norepinephrine synthesis in intact tissue by drugs and during short-term adrenergic nerve stimulation. Pharmacol. Rev. 24, 203–221 (1972).
Wurtman, R. J., Pohorecky, L. A., Baliga, B. S.: Adrenocortical control of the biosynthesis of epinephrine and proteins in the adrenal medulla. Pharmacol. Rev. 24, 411–426 (1972).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Snider, S.R., Carlsson, A. The adrenal dopamine as an indicator of adrenomedullary hormone biosynthesis. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 347–357 (1972). https://doi.org/10.1007/BF00501124
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00501124