Stimulation of hormone-responsive adenylate cyclase activity by a factor present in the cell cytosol

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Abstract
Homogenates of whole tissues were shown to contain both intracellular and extracellular factors that affected particulate adenylate cyclase activity in vitro. Factors present in the extracellular fluids produced an inhibition of basal, hormone- and F-stimulated enzyme activity but factors present in the cell cytosol increased hormone-stimulated activity with relatively little effect on basal or F-stimulated enzyme activity. The existence of this cytosol factor or factors was investigated using freshly isolated human platelets, freshly isolated rat hepatocytes, and cultured cells derived from rat osteogenic sarcoma, rat calvaria, mouse melanoma, pig aortic endothelium, human articular cartilage chondrocytes and human bronchial carcinoma (BEN) cells. The simulation of the hormone response by the cytosol factor ranged 60-890% depending on the tissue of origin of the adenylate cyclase. In each case the behavior of the factor was similar to the action of GTP on that particular adenylate cyclase preparation. No evidence of tissue or species specificity was found, as cytosols stimulated adenylate cyclase from their own and unrelated tissues to the same degree. In the human platelet, the inclusion of the cytosol in the assay of adenylate cyclase increased the rate of enzyme activity in response to stimulation by prostaglandin[PG]E1 without affecting the amount of PGE1 required for half-maximal stimulation or the characteristics of enzyme activation by PGE1.