Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.
The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal N-acetyltransferase (EC 2.3.1.5) and [3H]melatonin production was investigated in the rat. In vivo studies indicated that phenylephrine, an alpha-adrenergic agonist, potentiated and prolonged the effects of isoproterenol, a beta-adrenergic agonist. Similar observations were made in organ culture with glands devoid of functional nerve endings. In addition, a combination of 1 microM prazosin, an alpha 1-adrenergic blocking agent, and 1 microM propranolol, a beta-adrenergic blocking agent, was many times more potent then either agent alone in blocking the stimulatory effects of norepinephrine on N-acetyltransferase activity and [3H]melatonin production. These findings establish that norepinephrine acting through alpha- and beta-adrenergic receptors stimulates rat pineal N-acetyltransferase activity and, as a result, the production of melatonin. Apparently, beta-adrenergic activation is an absolute requirement, and an alpha-adrenergic receptor mechanism potentiates beta-adrenergic activation. These findings are significant because they demonstrate alpha-adrenergic potentiation of beta-adrenergic effects. In addition, they indicate that the widely held belief that melatonin production is regulated exclusively by a postsynaptic beta-adrenergic mechanism must be revised.
D000123:Acetyltransferases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002478:Cells, Cultured; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D007545:Isoproterenol