Forskolin stabilizes a functionally coupled state between activated guanine nucleotide-binding stimulatory regulatory protein, Ns, and catalytic protein of adenylate cyclase system in rat erythrocytes

Ca2+ channel currents in rat sensory neurones: interaction between guanine nucleotides, cyclic AMP and Ca2+ channel ligands.

“…GTPyS but not control IB.. Several factors may contribute to the effect of forskolin in the presence of GTPyS. Although forskolin activates the catalytic subunit of adenylyl cyclase and produces a small enhancement of cyclic AMP production even in cells lacking G. (Clark, Goka, Green, Barber & Butcher, 1982), its most prominent effect is to stabilize the complex of activated G. with adenylyl cyclase, allowing it to compete effectively with activated G, (Yamashita, Kurokawa, Higashi, Dan'ura & Ishibashi, 1986). Effects of forskolin have been reported which do not involve cyclic AMPdependent protein phosphorylation (for review see Laurenza, Sutkowski & Seamon, 1989), and for this reason experiments were designed to examine whether the forskolin-induced increase of IB, GTPys required phosphorylation.…”

Anesthetic Barbiturates Enhance Gsα‐Dependent Cyclic AMP Production in S49 Mouse Lymphoma Cells

“…This cycle occurs in the absence of agonist-occupied receptor but occurs at a much higher rate in its presence . Forskolin stimulates adenylyl cyclase in two ways ; i .e ., it stimulates the catalytic unit directly at a low-affinity site, and it enhances the interaction between Gs , and the catalytic unit of adenylyl cyclase at a high-affinity site (Barber and Goka, 1985;Seamon and Daly, 1986;Yamashita et al, 1986) . Pentobarbital did not enhance adenylyl cyclase activity in WT cells that were stimulated by forskolin, which suggests that pentobarbital and forskolin may activate adenylyl cyclase by similar effects on G s , .…”

“…The effect of pentobarbital in the presence of forskolin in cyc -cells is noteworthy because 2 pM pentobarbital had no effect in the presence of forskolin in WT cells . These observations are not contradictory, though, because the mechanism of stimulation of adenylyl cyclase by forskolin in cyccells is different from that in WT cells ; in cyc -cells, forskolin stimulates adenylyl cyclase only at the low-affinity site on the catalytic unit, whereas, in WT cells, it also enhances the interaction between Gsa and the catalytic unit (Barber and Goka, 1985 ;Seamon and Daly, 1986;Yamashita et al, 1986) . These results suggest that the effects of low concentrations of pentobarbital are mediated through Gsa and that pentobarbital can also enhance cAMP accumulation by a mechanism that is independent of Gs,; this second effect is observed only in the absence of G,, and requires higher concentrations of pentobarbital .…”

“…GppNHp and NaF-AIC1 3 both stimulate adenylyl cyclase by activating G s . Forskolin, a naturally occurring diterpine, stimulates adenylyl cyclase both by activating directly the catalytic moiety at a low-affinity binding site and by facilitating interactions between G_ and adenylyl cyclase at a high-affinity binding site (Barber and Goka, 1985 ;Seamon and Daly, 1986 ;Yamashita et al, 1986) . The effects of barbiturates on adenylyl cyclase in membranes prepared from rat brain suggest that these drugs inhibit the interaction of the stimulatory G protein with adenylyl cyclase (Dan'ura et al ., , 1987(Dan'ura et al ., , 1989 .…”

Polymorphism of Cyclic 3´,5´-Adenosine Monophosphate Stimulation in Rat Erythrocytes

“…After this step, the agonist-re ceptor complex couples with the catalytic subunit and guanosine nucleotide proteins of the adenylate cy clase. There are several guanosine nucleotide regula tory proteins that either support or suppress the production of cAMP [13,14]. Because of the multicomponent reaction, the polymorphism of the stimu lated cAMP production may be located at any of the before-mentioned components of the complex.…”