Photoneural regulation of the mammalian pineal gland

Abstract

Mammalian pineal function appears to be controlled primarily through the release of noradrenaline from the terminals of nerves whose cell bodies lie in the superior cervical ganglia. This is the final segment of the following neural pathway: retina----retinohypothalamic projection----suprachiasmatic nuclei----paraventricular nuclei----intermediolateral cell column----superior cervical ganglia----nervi conarii----pineal gland. Noradrenaline acts on pinealocytes through alpha- and beta-adrenoceptors in an atypical manner. Beta-Adrenergic activation is an absolute requirement for the stimulation of both cyclic AMP and cyclic GMP production, and by itself produces a sixfold increase in the former and a twofold increase in the latter. Alpha-Adrenergic activation potentiates the beta-adrenergic stimulation of cyclic AMP production 10-fold, and that of cyclic GMP production about 200-fold. The mechanism of alpha- and beta-adrenergic interaction is being examined, and progress is being made in understanding the adrenergic control of cyclic AMP. It appears that alpha-adrenergic agonists act through the alpha 1-subclass of adrenoceptors to stimulate phospholipid turnover and the production of a breakdown product of phosphatidylinositol, diacylglycerol. This compound promotes the association of protein kinase C with membranes, which leads to the marked phosphorylation of one protein. The precise identity of this protein remains a mystery. This interaction leads to a larger cyclic AMP response but does not appear to be involved in the mechanism of potentiation of the cyclic GMP response. Changes in chronic neural stimulation produce reciprocal changes in the magnitudes of cyclic AMP and cyclic GMP responses. Chronic denervation results in a supersensitive cyclic AMP response and nearly complete disappearance of the cyclic GMP response. This is termed 'see-saw' signal processing. All the available evidence indicates that melatonin production is regulated by cyclic AMP. This nucleotide not only increases the activity of serotonin N-acetyltransferase (more correctly called arylalkylamine N-acetyltransferase) but also stabilizes the enzyme and prevents its inactivation.