Epidermal surface receptors which link pharmacological mediators to the adenylate cyclase system

Abstract

The major purpose of our studies has been to investigate various stimulators of the epidermal adenylate cyclase system. We have recognized the occurrence of four distinct adenylate cyclase systems which respond respectively to catecholamine, histamine, prostaglandin and adenosine. The exposure of floating skin slices in vitro to a stimulator causes a rapid intracellular accumulation of cyclic AMP, which is always transient. Further addition of the same stimulator will not stimulate the same receptor system against the state of 'refractoriness'. The addition of any of the other stimulators can increase the cyclic AMP level. Furthermore, the fact that each stimulator can yield an 'additive' stimulatory effects leads to the conclusion that the epidermis has four distinctly specific and independent adenylate cyclase systems. Our recent investigations have been directed to the analyses of subunits of these skin surface receptor-adenylate cyclase systems. We used two experimental systems, i.e. one being a 'leaky' cell system in which its subunits such as receptor, GTP-regulatory protein and the catalytic unit (adenylate cyclase) are still linked together, and the other being independent preparations of the receptor and catalytic units (with GTP-regulatory protein). These systems allowed us to probe the cell membrane from the inside as well as from the outside. Some of the preliminary kinetic data are herein introduced.