Cyclic Adenosine 3′,5′-Monophosphate in Guinea Pig Cerebral Cortical Slices: III. FORMATION, DEGRADATION, AND REFORMATION OF CYCLIC ADENOSINE 3′,5′-MONOPHOSPHATE DURING SEQUENTIAL STIMULATIONS BY BIOGENIC AMINES AND ADENOSINE

Abstract

Abstract In guinea pig cerebral cortical slices, formation of both endogenous and radioactive cyclic adenosine 3',5'-monophosphate (cyclic AMP), the latter derived from intracellular nucleotides labeled during a prior incubation with radioactive adenine, may be stimulated by incubation with histamine, histamine-norepinephrine, adenosine, veratridine, and combinations of adenosine and biogenic amines, allowed to return to basal levels after washing, and then restimulated by the same agent or a different agent. Restimulations by histamine or histamine-norepinephrine are minimal except in the presence of adenosine. Maximal accumulations of total cyclic AMP and of radioactive cyclic AMP decline slowly and in parallel during a series of repetitive stimulations with adenosine-histamine-norepinephrine. The results provide no evidence for significant translocation of nucleotides of different specific activities between morphological compartments of brain slices during repetitive stimulations of cyclic AMP formation. An intermediate incubation of slices with adenosine does not restore the responsiveness of the cyclic AMP-generating system to biogenic amines after a prior stimulation with histamine or histamine-norepinephrine. Part of the lack of response to biogenic amines after a prior stimulation by the same amines is apparently due to an increase in phosphodiesterase-mediated degradation of cyclic AMP since the addition of phosphodiesterase inhibitors partially restores the response to the biogenic amines. The presence of adenosine markedly decreases the rate of disappearance of cyclic AMP in slices after a prior stimulation with adenosine-histamine.