Summary
The adrenomedullary hormone release induced by physostigmine 0.5 to 1 mg/kg i.p. in rats was markedly potentiated by the α-adrenergic blocking agent phentolamine. This drug combination caused a considerable elevation of adrenal dopamine, a decrease in adrenalβ-hydroxylated catecholamines and an increase in plasma catecholamine levels. The monoexponential disappearance of dopamine after treatment with α-methyltyrosine was accelerated by physostigmine plus phentolamine, which thus seem to increase the rate of dopamine synthesis considerably, presumably by activating tyrosine hydroxylase.
Spinal transection at C7 caused a decrease in adrenal dopamine, an increase inβ-hydroxylated catecholamines and a decrease in plasma catecholamine levels. Moreover, the actions of physostigmine and phentolamine described above were completely prevented. These effects are thus presumably mediated via supraspinal centers. Chlorisondamine and atropine prevented the adrenomedullary hormone release induced by physostigmine plus phentolamine but did not, or only partially, prevent the increase in adrenal dopamine.
It is concluded that physostigmine plus phentolamine, like insulin, appear to stimulate a neurogenic mechanism leading to an activation of adrenomedullary tyrosine hydroxylase. This mechanism appears to operate independently of adrenomedullary hormone release and may stimulate catecholamine synthesis even at elevated adrenal catecholamine levels, suggesting that end-product inhibition of tyrosine hydroxylase is not of major importance. The neurogenic control of adrenomedullary synthesis does not seem to involve nicotinic or muscarinic receptors in the adrenal medulla; possibly a non-cholinergic mechanism operates at this level.
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The main results of this paper were reported at the III. International Catecholamine Symposium, Strasbourg 1973 (seeCarlsson et al., 1973).
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Carlsson, A., Lindqvist, M. Studies on the neurogenic short-term control of adrenomedullary hormone synthesis. J. Neural Transmission 35, 181–196 (1974). https://doi.org/10.1007/BF01258950
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DOI: https://doi.org/10.1007/BF01258950