Catecholamine-Stimulated Cyclic GMP Accumulation in the Rat Pineal: Apparent Presynaptic Site of Action

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 73; no. 10; pp. 3398 - 3402
• Main Authors: O'Dea, Robert F., Zatz, Martin
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.10.1976; National Acad Sciences
• Subjects: Acetylcholine - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Agonists; Animals; Calcium; Calcium - pharmacology; Carbachol - pharmacology; Catecholamines; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Cyclic nucleotides; Denervation; Dose-Response Relationship, Drug; Isoproterenol - pharmacology; Kinetics; Male; Melatonin - pharmacology; Nerves; Norepinephrine - pharmacology; Ouabain - pharmacology; Physiological regulation; Pineal gland; Pineal Gland - metabolism; Potassium; Potassium - pharmacology; Propranolol - pharmacology; Rats; Receptors; Receptors, Adrenergic - metabolism; Receptors, Adrenergic, alpha - metabolism; Sotalol - pharmacology; Stereoisomerism; Synaptic Membranes - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.10.3398

Guanosine 3′:5′-cyclic monophosphate (cGMP) increased 7-fold in rat pineal glands incubated in the presence of l-norepinephrine. This response consisted of two components-one was stereospecific and inhibited by α -adrenergic antagonists while the other was not stereospecific and not readily inhibited by antagonists. Although l-isoproterenol was more potent than l-norepinephrine it had less intrinsic activity and its action was not stereospecific. The increase in cGMP caused by these catecholamines, unlike that of adenosine 3′:5′-cyclic monophosphate (cAMP), was dependent upon extracellular calcium. Ouabain and high levels of potassium produced a marked, calcium-dependent increase in pineal cGMP, without affecting cAMP. There was no effect of cholinergic agonists on cGMP. Surgical denervation markedly reduced the cGMP response to stimulation by l-norepinephrine, potassium, or ouabain. This was in contrast to the enhanced response of cAMP in denervated glands. The nonspecific increase in cGMP caused by l-isoproterenol, however, was not affected by denervation. These data demonstrate the existence of a calcium-dependent presynaptic mechanism for the generation of cGMP which may be mediated by an α -adrenergic-like receptor. In addition, the mechanisms regulating pineal cGMP appear to be physiologically distinct from those regulating cAMP.