Accumulation of adenosine 3',5'-monophosphate in rat brain slices: effects of prostaglandins. |
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Authors: | K Dismukes J W Daly |
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Institution: | National Institute of Arthritis, Metabolism, and Digestive Diseases National Institutes of Health Bethesda, Maryland 20014, USA |
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Abstract: | Prostaglandin E1 and E2 and 15(S)-15-methyl PGE2 methyl ester stimulate the accumulation of radioactive cyclic AMP in brain slices from Sprague-Dawley rats, labelled during a prior incubation with 14C] adenine. Prostaglandins A1 and B1 have marginal effects and prostaglandin F1α has no effect. Relatively high concentrations of about 80 μM PGE1, PGE2 and 15(S)-15-methyl PGE2 are required to elicit a maximal 2–5 fold increase in accumulation of cyclic AMP in slices from cerebrum, but significant increases are elicited by 3.5 μM prostaglandin. Similar increases are elicited in slices from neocortex, striatum or midbrain-thalamus-hypothalamus, while lesser increases pertain in slices from cerebellum, medulla-pons or hippocampus. The accumulation of cyclic AMP elicited by PGE1 in slices from cerebrum was not blocked by naloxone, propranololphentolamine, tetracaine, theophylline, or by nearly equimolar concentrations of either of two prostaglandin antagonists, 7-oxa-13-prostynoic acid and the dibenzoxazepine hydrazide, SC 19220. Morphine potentiated the effects of PGE1. The combination of 85 μM PGE1 with either isoproterenol, norepinephrine, adenosine or veratridin did not increase the accumulation of cycli AMP significantly above those elicited by the isoproterenol, norepinephrine, adenosine or veratridine alone. The combined effect of PGE1 and norepinephrine in the presence of a β-adrenergic antagonist, sotalol, was, however, additive. The results indicate that PGE1 stimulates cyclic AMP formation in rat brain slices, but that it either has antagonist activity with respect to accumulations of cyclic AMP-elicited by other agents or has no detectable agonist activity when cyclases are maximally stimulated by other agents. |
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