Search

Substance P, forskolin and isoprenaline stimulated rat parotid alpha-amylase secretion in vitro. Synergistic responses were observed with combinations of any two of the three secretagogues such that subthreshold doses of one caused a pronounced shift in the dose-response curve to the second. This potentiation of secretion could neither be explained by an interaction at the receptor recognition binding site, as identified by ligand binding, nor wholly by interactions in second messenger systems. Thus forskolin and isoprenaline were unable to alter substance P-induced changes in phosphatidylinositol metabolism. Similarly substance P was without effect on forskolin or isoprenaline-stimulated cAMP production. In contrast the potentiation of isoprenaline-induced amylase secretion by forskolin was preceded by a marked enhancement of cAMP production suggesting that the activation of the adenylate cyclase complex is reflected in the cellular response.

[3H]Forskolin bound to high- and low-affinity sites in the rat brain. The high-affinity site was discretely located, with highest densities in the striatum, nucleus accumbens, olfactory tubercule, substantia nigra, hippocampus, and the molecular layers of the cerebellum. This site did not correlate well with the distribution of adenylate cyclase. The high-affinity striatal binding site may be associated with a stimulatory guanine nucleotide-binding protein. Thus, the number of sites was increased by the addition of Mg2+ and guanylyl imidodiphosphate. Cholera toxin stereotaxically injected into one rat striatum increased the number of binding sites, and no further increase was noted following the subsequent addition of guanyl nucleotide. High-affinity forskolin binding sites in non-dopamine-rich brain areas (hippocampus and cerebellum) were modulated in a qualitatively different manner by guanyl nucleotides. In these areas the number of binding sites was significantly reduced by the addition of guanyl nucleotide. These results suggest that forskolin may have a potential role in identifying different functional/structural guanine nucleotide-binding proteins.