Sensitivity and Cyclic Nucleotides in the Rat Pineal Gland
β-adrenergic stimulation induces serotonin N-acetyltransferase (SNAT) activity in the rat pineal gland. The magnitude and some of the characteristics of this response vary as a function of the gland’s previous exposure to stimulation. A period of stimulation results in a subsensitive response to subsequent stimulation. A period without stimulation provides a super-sensitive response to subsequent stimulation. Investigations concerned with the mechanisms regulating the rat pineal’s sensitivity to β-adrenergic stimulation are described. These have focused on the regulation of cyclic AMP metabolism. Several of the components involved in the induction of SNAT activity appear to participate in the regulation of sensitivity. These include the β-adrenergic binding sites, the catecholamine-sensitive adenylate cyclase, the cyclic nucleotide Phosphodiesterase, and the cyclic AMP-dependent protein kinase. Thus, the rat pineal’s sensitivity to β-adrenergic stimulation appears to be regulated at multiple sites. Other investigations have focused on the regulation of pineal cyclic GMP metabolism. Unlike cyclic AMP, the stimulation of cyclic GMP synthesis requires the presence of intact nerve endings and of extracellular calcium. Some of the characteristics of pineal cyclic GMP regulation are described.
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- Goldberg, N. D., Haddox, M. K., Nicol, S. E., Glass, D. B., Sanford, C. H., Kuehl, F. A., Estensen, R.: Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the yin yang hypothesis. In: Advances in Cyclic Nucleotide Research, Vol. 5 (Drummond, G. I., Greengard, P., Robison, G. A., eds.), pp. 307–330. New York: Raven Press. 1975.Google Scholar
- Klein, D. C., Weller, J.: The role of N-acetylserotonin in the regulation of melatonin production. Fourth International Congress of Endocrinology, Abstracts. Excerpta Medica Int. Congr. Ser. 256, 52 (1972 a).Google Scholar
- Klein, D. C., Weiler, J.: Adrenergic adenosine 3′, 5′-monophosphate regulation of serotonin N-acetyltransferase activity and the temporal relationship of serotonin N-acetyltransferase activity to synthesis of 3H-N-acetylserotonin and 3H-melatonin in cultured rat pineal. J. Pharm. Exp. Ther. 186, 516–527 (1973).Google Scholar
- O’Dea, R. F., Gagnon, C., Zatz, M.: Regulation of cyclic GMP in the rat pineal and posterior pituitary glands. J. Neurochem. (in press, 1978).Google Scholar
- Weiss, B., Costa, E.: Selective stimulation of adenyl cyclase activity in rat pineal by pharmacologically active catecholamines. J. Pharm. Exp. Ther. 161, 310–319 (1968 a).Google Scholar
- Wurtman, R. J., Axelrod, J., Kelly, D.: The pineal. New York: Academic Press. 1968.Google Scholar
- Zatz, M., O’Dea, R. F.: Regulation of protein kinase in rat pineal: increased Vmax in supersensitivity glands. J. Cyc. Nuc. Res. 2, 427–439 (1976).Google Scholar
- Zatz, M., Kebabian, J. W., Romero, J. A., Lefkowitz, R. J., Axelrod, J.: Pineal β-adrenergic receptor: correlation of binding of 3H-alprenolol with stimulation of adenylate cyclase. J. Pharm. Exp. Ther. 196, 714 to 722 (1976 a).Google Scholar