The Pharmacology of the Pineal Gland

Abstract

Only recently have a sufficient number of publications been available to legitimize a review of the pharmacology of the mammalian pineal organ. Two decades ago Kitay & Altschule reviewed the world literature on pineal physiology, which comprises several thousand papers, and concluded only that removal of the pineal, or administration of pineal extracts, somehow affected pigmentation in lower vertebrates and gonadal function in mammals (1). As the studies described below demonstrate, much more information is now available concerning the pharmacology of the pineal. This review subdivides present knowledge into two areas: (a) the effects on mammals of administering pineal extracts or pure synthetic or natural pineal constituents and (b) the effects of drugs and hormones on the pineal itself. As might be anticipated, the bulk of studies cited in both categories deals with the pineal hormone, melatonin. Melatonin was first isolated from bovine pineal extracts in 1958 by Lerner and his colleagues (2), who used as a marker the capacity of the hormone to aggregate the pigment granules in amphibian melanophores around the cell nucleus. Five years later, Wurtman et al (3) showed that melatonin affected a physiological function in mammals, that is, the size and secretion of the ovary, and subsequent studies have demonstrated that melatonin administration also modifies the growth, composition, and functional activities of numerous other organs. Only recently an assay was developed that allows quantification of the melatonin in human urine (4). The concentrations of the compound vary with a characteristic daily rhythm, peaking at night. The pineal's apparent role as the sole or major source of melatonin, the presence of melatonin in urine, and the demonstration that physiologic effects follow a pinealectomy or the administration of melatomin seem to justify labeling it a pineal hormone. Melatonin synthesis and pineal biosynthetic activity are generally controlled by the sympathetic nerves of this organ (5,6). Therefore, it should not be surprising that drugs known to modify the synthesis, release, or metabolism of norepinephrine in peripheral organs also affect pineal function. Melatonin is itself a derivative of another biogenic amine, serotonin, whose metabolism and actions are also affected by numerous drugs. Indeed, the pineal has often provided an apt tool for examining monoaminergic mechanisms for pharmacologists not specifically concerned with its particular functional properties.

Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells.

“…Norepinephrine promotes Na+ retention by a mechanism involving a-adrenergic, but not 3-adrenergic (2-4), receptor activation. Activation of a-adrenergic receptors is associated with increased cytosolic calcium in many cell types (5,6). Here we present evidence that norepinephrine, acting on a-adrenergic receptors, increases Na+,K+-ATPase activity in permeabilized cells of the proximal convoluted tubule of rat kidney.…”

Potential role of tryptophan and chloride in the inhibition of human myeloperoxidase

“…Tryptophan serves as a biosynthetic precursor for a wide variety of indole-containing metabolites, which are involved in a large and essential number of physiological functions [68]. For example, it increases levels of serotonin on the brain as well as melatonin [69]. It is tempting to speculate that under normal condition, there is a balance between levels of MPO Working kinetic model for Trp interactions with MPO.…”

G protein-coupled receptors regulate Na+,K+-ATPase activity and endocytosis by modulating the recruitment of adaptor protein 2 and clathrin

“…We chose to study in renal epithelial cells the effect of Oxy, a compound postulated to counteract the effect of DA on NKA activity by activating protein phosphatases (24). Oxy action is mediated by activation ␣ 1 and ␣ 2 adrenergic receptors, and the cellular responses to it has been associated, depending on the tissue, with increased intracellular calcium (30) and with negative coupling to adenylyl cyclase. (31,32).…”