Stimulation of brain adenylate cyclase activity by the undecapeptide substance P and its modulation by the calcium ion.

Synthetic substance P stimulated adenylate cyclase activity in particulate preparations from rat and human brain. The concentration of substance P for half maximal stimulation in rat brain was 1.8-10-minus 7 M. The stimulatory effect of substance P on the rat brain adenylate cyclase activity was 88% compared with 48% by noradrenalin, 163% by prostaglandin E1 and 184% by prostaglandin E2. Both the basal and substance P-stimulated adenylate cyclase activity in rat brain were inhibited by concentration of Ca-2+ above 10-minus 6 M. The chelating agent ethyleneglycol-bis-(beta-aminoethylether)-N, N'-tetraacetic acid at a concentration of 0.1 mM reduced the basal adenylate cyclase activity by 64% and eliminated the substance P-stimulated activity. The inhibition by ethyleneglycol-bis-(beta-aminoethylether)-N, N'-tetraacetic acid was completely reversed by increasing concentrations of Ca-2+.