Effect of depolarizing agents on accumulation of cyclic adenosine 3′, 5′-monophosphate in cerebral cortical slices
European Journal of PharmacologyPublished 1 February 1972
Hirotoshi Shimizu, John W. Daly
Citations74
SJR quartileQ1
SJR score1.20
SNIP0.98
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TL;DR
The hypothesis that depolarizing agents elevate levels of cyclic AMP at least in part by a depolarization-evoked ‘release’ of adenosine, which then interacts with a regulatory unit for adenyl cyclase is supported.
Abstract
Agents such as K+, NH4+, ouabain, batrachotoxin and veratridine, which are known to cause depolarization of electrically excitable membranes, cause an accumulation of cyclic 14C-AMP in incubated slices of cerebral cortex. The effect of depolarizing such agents on cyclic 14C-AMP formation and on 14C-acetyl choline release is blocked by 'membrane stabilizers' such as cocaine. The effects of batrachotoxin and veratridine are completely blocked by tetrodotoxin. The effect of increasing concentrations of K+ on accumulation of cyclic 14C-AMP correlates with changes in membrane potential, rather than with stimulation of cellular metabolism. The effect of veratridine on accumulation of cyclic 14C-AMP is not blocked under conditions where malonate inhibits stimulation of cellular metabolism. Ouabain, veratridine and batrachotoxin do not inhibit cyclic 3′, 5′-phosphodiesterase at the concentrations in which they are effective in causing accumulation of cyclic 14C-AMP. The data support the hypothesis that depolarizing agents elevate levels of cyclic AMP at least in part by a depolarization-evoked ‘release’ of adenosine, which then interacts with a regulatory unit for adenyl cyclase.
Keywords
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