Specific refractoriness of adenylate cyclase in skin to epinephrine,prostaglandin E,histamine and AMP

The cyclic AMP level in pig skin (epidermis) increases markedly after incubation with epinephrine, prostaglandin E, histamine or adenosine 5′-monophosphate. This increase is transient and “spiking” is the consistent response to these four stimulators. The “spiking” is due to a non-responsiveness or refractoriness which develops within minutes and is specific to any one stimulating hormone but not to the others. The addition of inhibitors of protein syntheses did not prevent the development of the refractoriness. Adenylate cyclase and phosphodiesterase activities measured in skin homogenates prepared from skin samples taken before, during and after the “spiking” did not change significantly. The hormone-induced refractoriness in this skin system appears to be due to a specific, localized loss of function of the adenylate cyclase system.