The Effect of Ischemia on Cyclic Adenosine 3′,5′-Monophosphate Accumulation in Mouse Skin

The incubation of adult mouse skin pieces in a buffered salts medium at 37°C led to a rapid accumulation of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in the tissue. In mouse skin maximum accumulation occurred after 2min incubation; levels reverted to near control levels after a further 7min incubation. The increase in cyclic AMP contents of the skin pieces was probably not due to the release of materials which activate adenylate cyclase after binding to cellular receptors. Thus, cyclic AMP accumulation was unaffected by the inclusion of α- or β-adrenergic antagonists, or by the pretreatment of adult mouse skin with indomethacin (an inhibitor of prostaglandin synthetase). Furthermore, adenosine, a known activator of epidermal adenylate cyclase, could not be detected in the incubation medium. The functional integrity of epidermal adenylate cyclase was maintained during the cyclic AMP accumulation in response to ischemia. Thus, adenosine, histamine, isoproterenol and prostaglandin E2 (PGE2) augmented the cyclic AMP response. Cyclic AMP accumulation at 37°C was not observed in newborn mouse skin; this lack of cyclic AMP accumulation was probably not due to increased activity of low affinity cyclic AMP phosphodiesterase in newborn mouse skin