Forskolin-stimulated activity

The role of plasma adenosine in the forskolin-stimulating activity on platelet cAMP has been studied (8) (Figure 4). Platelet cAMP levels decrease by about 30% after depletion of plasma adenosine. Forskolin (3 pM) induces a 3-fold increase in platelet cAMP in PI containing normal levels of adenosine, whereas only a 1.5 fold increase in platelet cAMP levels is seen in adenosine-depleted PRP. Similar effects of plasma... 

Fig. 8. Enhanced signaling of the a2ALys251 polymorphic receptor. Adenylyl cyclase activities were determined in the presence of 5.0 pM forskolin and the indicated concentrations of the full agonist epinephrine. Results as shown are the percentage inhibition of forskolin-stimulated activities from clones at matched levels of expression (-2500 fmol/mg)., p < 0.05 for the maximal inhibition compared with wild-type for both agonists. (From ref. 22 with permission.)...

Not all opiates induce an increase in forskolin stimulation of adenylyl cyclase. Buprenorphine, which is used to treat morphine dependence, does not cause a compensatory rise in cyclase activity [80]. Co-treatment of morphine with buprenorphine prevented morphine from increasing cyclase activity suggesting that bu-... 

The corrector activity of 15 was not limited to recombinant systems as it was confirmed in cultured HBE cells isolated from F508del homozygous patients. After 48-h incubation with 6.7 pM 15, a 2-fold increase in forskolin-stimulated chloride current (compared to DMSO-treated cells) or 14% of the response obtained in non-CF-HBE was observed. It was also reported that 14 and 15 increase the cell surface density of other trafficking-deficient proteins, including G601S-hERG. The authors speculate that this class of compounds may act on the folding pathway shared by both misfolded proteins rather than on CFTR itself [16]. 

Fig. 12.4 Functional coupling of the Gly389 and Arg389 receptors to adenylyl cyclase. (Reproduced from ref. 26 with permission of the American Society for Biochemistry and Molecular Biology.) Shown are the results from studies with clonal lines expressing each receptor at matched levels and the data presented as absolute activities (A) and normaUzed to the stimulation by forskolin (B). The results of similar studies with two other clonal lines are shown in C and D. The Arg389 demonstrated small increases in basal activities and marked increases in agonist-stimulated activities compared with the Gly389 receptor. Shown are the mean results from four independent experiments carried out with each line. Absent error bars denote that standard errors were smaller than the plotting symbol...

An inhibitory effect of 8-OH-DPAT on forskolin-stimulated adenylyl cyclase activity is observed in hippocampal membranes of the guinea pig and rat, and has been used as an index of the functional activities of 5-HTIA receptors [178]. Cold stress induces a reduction of the inhibitory effect of 8-OH-DPAT in the hippocampus isolated from 18-month-old rats, although it has no influence on either the affinity or number of [3H]8-OH-DPAT binding sites. The administration of EGb (50 mg/kg p.o. for 14 days) prevents the cold stress-induced reduction in the inhibitory effect of 8-OH-DPAT on forskolin-stimulated adenylyl cyclase activity in old rats. These results indicate that EGb prevents the stress-induced desensitization of hippocampal 5-HTu receptors thus, its effects might explain anti-stress and antidepressant properties of EGb [177]. 

AC = stimulates adenylate cyclase activity -AC = inhibits forskolin-stimulated adenylate cyclase activity PI = stimulates phosphatidylinositol (PI) hydrolysis. 

De Vivo M, Maayani S. Characterization of the 5-hydroxytryptaminela receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther 1986 238 248-253. 

The 5-HT1B receptors are predominantly localized at the presynaptic level, they are coupled negatively to adenylate cyclase, and their activation by selective agonists induces a decrease in the forskolin-stimulated adenylate cyclase (156) for review, see ref. 157. Consequently, their activation reduces neurotransmitter release (see below). 

In non-CF HBE, forskolin stimulated a large, biphasic increase in Cl" secretion, whereas the response in AF508-HBE was monophasic and <5% of the wild-type response. The forskolin response in non-CF and AF508-HBE is blocked by CFTR inhibitors but not the Ca2+-activated Cl" channel blocker, DIDS, indicating that the response is due to CFTR activity in the apical membrane. Residual AF508-CFTR activity in the apical membrane of CF airway... 

Consistent with the sequence similarities between the ORLl and opioid receptors, activation of the ORLl receptor triggers the same signal transduction mechanisms as used by the opioid receptors. Thus activation of ORLl receptors inhibits both forskolin-stimulated adenylyl (yclase and currents and activates several other effectors, including inward rectifying channels, protein kinase C, mitogen-activated protein kinase (MAP kinase) and phospholipase C (see Ref 89 for a review). 

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