Catecholamine-stimulated cyclic GMP accumulation in the rat pineal: apparent presynaptic site of action.
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 alpha-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 stereospecifc. 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 alpha-adrenergic-like receptor. In addition, the mechanisms regulating pineal cGMP appear to be physiologically distinct from those regulating cAMP.
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013015:Sotalol / Q000494:pharmacology; D013237:Stereoisomerism; D013570:Synaptic Membranes / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010042:Ouabain; D002217:Carbachol; D011433:Propranolol; D013015:Sotalol; D000242:Cyclic AMP; D006152:Cyclic GMP; D008550:Melatonin; D007545:Isoproterenol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine