Guanine nucleotides regulate the effect of substance P on striatal adenylate cyclase of the rat.

Substance P was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Substance P did not influence basal adenylate cyclase activity or the stimulation of the enzyme by dopamine. No influence of substance P was seen on the effects of calcium and magnesium chloride as a cofactor of adenylate cyclase. Also the inhibition of adenylate cyclase activity by the dopamine antagonist fluphenazine was not influenced by substance P. However, substance P was able to enhance cyclic AMP formation in the presence of guanosine-imidodiphosphate (Gpp(NH)p), whereas the stimulatory effect of guanosine-triphosphate (GTP) was inhibited by substance P. In our study we suggest that substance P interacts with the guanine nucleotide regulatory subunit without directly affecting D-1 dopamine receptors in the caudate-putamen of the rat.