Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in striatal membranes from desipramine (DMI)-treated rats (10 mg/kg, b.i.d., for 5 days). GPT exerted the same biphasic effect on basal and DA-stimulated enzyme activity in membranes from DMI-treated rats as on saline-treated rats. Rats were injected intraventricularly once with islet activating protein (IAP), pertussis toxin, and given extended treatment with DMI in order to study the effects on the inhibitory GTP-binding protein (Gi). Gi loses its function as a signal transducer on being ADP-ribosylated selectively by the IAP. D2 inhibition of adenylate cyclase by DA was attenuated by the IAP treatment in both DMI-and saline-treated rats; peak levels of DA plus GTP stimulation shifted from 1 microM to 100 microM GTP. D1 stimulation of adenylate cyclase by DA was also attenuated by the IAP in the DMI-treated rats. Since long-term treatment with DMI (15 mg/kg, once a day, for 3 weeks) resulted in suppression of D1 stimulation similar to that seen in the present findings, uncoupling between D2 receptors and Gi due to IAP treatment might accelerate DMI-induced adaptive changes of dual control of adenylate cyclase system by DA.
J Neural Transm Gen Sect 1994
PMID:Acceleration of desipramine-induced changes on the dopamine receptor-coupled adenylate cyclase system by pertussis toxin. 773 10

Adenylate cyclase sensitivity to neurohypophyseal hormones was investigated in isolated glomeruli and in nephron segments microdissected from collagenase-treated kidneys of Rana ridibunda. Vasotocin treatment increased adenylate cyclase activity in glomeruli and in collecting ducts and did not modify it in proximal convoluted tubules and in early and late distal tubules. In glomeruli, the hormonal stimulation resulted mainly in a decrease in the Km value for adenylate cyclase, which means a higher affinity for substrate (ATP) to the enzyme, whereas the response to forskolin was accounted for by increases both in affinity for substrate and in maximal adenylate cyclase velocity. The homologous neurohypophyseal hormones stimulated frog glomerular adenylate cyclase with the following rank order of affinities: hydrin 1 > or = AVT = AVP > or = hydrin 2 > OT > or = mesotocin > isotocin; structural analogs dDAVP, VDAVP, dVDAVP, and [Phe2,Orn8]VT had weak agonistic properties, [Thr4,Gly7]OT was inactive, and the antagonists OVTA, d(CH2)5Tyr(Et)2VAVP, and des-Gly9-d(CH2)5Tyr(Et)2VAVP inhibited hormone-induced enzyme activation with similar apparent inhibition constants. The vasotocin receptors triggering adenylate cyclase stimulation in frog glomeruli differ pharmacologically from V2 vasopressin receptors of mammalian kidneys and may also differ from V2-like vasotocin receptors of amphibian skin and urinary bladder.
Gen Comp Endocrinol 1995 Apr
PMID:Vasotocin-sensitive adenylate cyclase in frog glomeruli. 778 59

Age-related alterations in binding sites of major second messengers and a selective adenosine 3',5'-cyclic monophosphate (cyclic-AMP) phosphodiesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]forskolin, [3H]cyclic-AMP, and [3H]rolipram were used to label protein kinase C (PKC), IP3 receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca2+/calmodulin-independent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [3H]PDBu binding was significantly reduced in the hippocampal CA1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [3H]IP3 binding revealed significant elevations in the nucleus accumbens, hippocampal CA1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [3H]Forskolin binding in middle-aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [3H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [3H]rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP3, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclic-AMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that intracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits.
J Neural Transm Gen Sect 1994
PMID:Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain. 787 23

Using pseudopregnant rat ovaries, the possibility was examined whether hCG-induced early desensitization of the LH/hCG receptor was accompanied by changes in the physical state of membranes. Thirty min after a single s.c. injection of 75 IU hCG, the hCG-responsive adenylylcyclase activity was reduced, whereas hCG binding to ovarian membranes was still normal. Membrane lipid rigidity, as determined by fluorescence polarization of DPH, decreased as early as 30 min after injection of a desensitizing dose of hCG. There was no difference in membrane rigidity when ovarian membranes were incubated 0.5 or 2 h with hCG or LH. The decrease of membrane lipid rigidity in the process of rapid desensitization of rat luteal tissue does not appear to be associated with protein synthesis. Desensitization also modified the differential scanning calorimetric profile. The results indicate that hCG-induced changes in the physical state of rat ovary membranes are preceded by the process of desensitization.
Gen Physiol Biophys 1994 Aug
PMID:Changes in physical properties of ovarian membranes after hCG-induced desensitization in rats. 789 Jan 46

1. Bradykinin and related kinins possess two different types of action (consisting of relaxation and contraction) in the isolated rat duodenum via their specific receptors. However, the mechanisms of these actions have not been fully elucidated. The present study was undertaken to investigate the effects of the agents affecting cyclic nucleotide metabolism on bradykinin-induced relaxations and on bradykinin- and des-Arg9-bradykinin-induced contractions. 2. Des-Arg9-bradykinin, B1 receptor agonist, and high concentrations of bradykinin elicited dose-dependent contractile responses in the rat duodenum, while low concentrations of bradykinin caused a dose-dependent relaxation in this tissue. 3. Nicotinic acid, an inhibitor of adenylate cyclase, inhibited the relaxation of rat duodenum induced by bradykinin at low concentrations in a non-competitive manner. However, the inhibitory efficacy of nicotinic acid against bradykinin was limited by 39.9% and this inhibition was not further increased by higher concentrations of nicotinic acid up to 10(-3) M. 4. Imidazole, an activator of cyclic nucleotide phosphodiesterase, caused a slight inhibition of the relaxant responses to low concentrations of bradykinin and of the contractile responses to des-Arg9-bradykinin and high concentrations of bradykinin in isolated rat duodenum. These inhibitions were also limited in efficacies and not increased by higher concentrations of imidazole. 5. Methylene blue, an agent that inhibits soluble guanylate cyclase, suppressed the contractions of rat duodenum induced by des-Arg9-bradykinin and high concentrations of bradykinin in a non-competitive manner. Again, these inhibitions were limited and further increase in the inhibitory efficacy was not observed in spite of increasing the methylene blue concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Gen Pharmacol 1994 Nov
PMID:Effects of the agents affecting cyclic nucleotide metabolism on the bradykinin- and des-Arg9-bradykinin-induced relaxations and contractions in isolated rat duodenum. 789 50

Unlike mammals, the goldfish is unique in having dopamine (DA) D1 receptors in the anterior pituitary. In this species, DA stimulates growth hormone (GH) release via D1 receptors coupled to the cAMP-dependent pathway. To further examine the postreceptor mechanisms of this novel pituitary DA D1 system, the role of extracellular Ca2+ ([Ca2+]e] in mediating DA D1-stimulated GH release was studied using dispersed goldfish pituitary cells. The GH responses to DA (1 nM-10 microM), the D1 agonist SKF38393 (1 microM), and the Ca2+ ionophore A23187 (10 microM) were abolished by incubation with Ca(2+)-deficient medium. Incubation with depolarizing doses of KCl (10-25 mM), which activate voltage-sensitive Ca2+ channels (VSCC), induced GH release in a dose-dependent manner. In contrast, the VSCC blockers nifedipine (10 microM), nicardipine (10 microM), and verapamil (10 microM) and the inorganic competitor of Ca2+ entry CoCl2 (5 mM) blocked the GH responses to DA (1 microM) as well as SKF38393 (1 microM). These results strongly indicate that the entry of [Ca2+]e via VSCC is an essential part of the signal transduction mechanisms mediating DA D1-stimulated GH release in the goldfish. In this study, the possible interactions between the Ca(2+)- and cAMP-dependent pathways in DA-induced GH secretion were also investigated. The membrane-permeant cAMP analogue 8Br.cAMP (1 mM) and the adenylate cyclase activator forskolin (10 microM) stimulated GH release from goldfish pituitary cells. These GH responses were suppressed by incubation with Ca(2+)-deficient medium or with the VSCC blocker nifedipine (10 microM). Furthermore, the GH responses to forskolin (10 microM) and the nonselective DA agonist apomorphine (1 microM) were not additive to that of the Ca2+ ionophore A23187 (10 microM). These results suggest that [Ca2+]e entry induced by DA D1 stimulation occur at steps after activation of the cAMP-dependent pathway.
Gen Comp Endocrinol 1994 Jun
PMID:Entry of extracellular calcium mediates dopamine D1-stimulated growth hormone release from goldfish pituitary cells. 792 40

Effects of neurotransmitters on cAMP-mediated signal transduction in frog olfactory receptor cells (ORCs) were studied using in situ spike recordings and radioimmunoassays. Carbachol, applied to the mucosal side of olfactory epithelium, amplified the electrical response of ORCs to cAMP-generating odorants, but did not affect unstimulated cells. A similar augmentation of odorant response was observed in the presence of phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC). The electrical response to forskolin, an activator of adenylate cyclase (AC), was also enhanced by PDBu, and it was attenuated by the PKC inhibitor Goe 6983. Forskolin-induced accumulation of cAMP in olfactory tissue was potentiated by carbachol, serotonin, and PDBu to a similar extent. Potentiation was completely suppressed by the PKC inhibitors Goe 6983, staurosporine, and polymyxin B, suggesting that the sensitivity of olfactory AC to stimulation by odorants and forskolin was increased by PKC. Experiments with deciliated olfactory tissue indicated that sensitization of AC was restricted to sensory cilia of ORCs. To study the effects of cell Ca2+ on these mechanisms, the intracellular Ca2+ concentration of olfactory tissue was either increased by ionomycin or decreased by BAPTA/AM. Increasing cell Ca2+ had two effects on cAMP production: (a) the basal cAMP production was enhanced by a mechanism sensitive to inhibitors of calmodulin; and (b) similar to phorbol ester, cell Ca2+ caused sensitization of AC to stimulation by forskolin, an effect sensitive to Goe 6983. Decreasing cell Ca2+ below basal levels rendered AC unresponsive to stimulation by forskolin. These data suggest that a crosstalk mechanism is functional in frog ORCs, linking the sensitivity of AC to the activity of PKC. At increased activity of PKC, olfactory AC becomes more responsive to stimulation by odorants, forskolin, and cell Ca2+. Neurotransmitters appear to use this crosstalk mechanism to regulate olfactory sensitivity.
J Gen Physiol 1993 Feb
PMID:Protein kinase C sensitizes olfactory adenylate cyclase. 809 69

For the present study, calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA) were used to investigate the possible roles that changes in intracellular calcium content and protein kinase C activation play in steroid production by goldfish vitellogenic ovarian follicles (0.2-0.7 mm in diameter) incubated in vitro. While largely ineffective when tested alone, PMA and A23187 exhibit synergism leading to increased testosterone and 17 beta-estradiol production. Production of both steroids was also increased by the addition of either human chorionic gonadotropin (hCG) or forskolin, a direct activator of adenylate cyclase. However, hCG- and forskolin-stimulated testosterone and 17 beta-estradiol production was attenuated by PMA and A23187 either alone or in combination. Both drugs blocked the stimulatory actions of hCG on adenosine 3',5'-cyclic monophosphate (cAMP) formation. PMA also influenced steroid production at sites distal to cAMP formation as it blocked the actions of dibutyryl cAMP a permeant analog of cAMP. This action was prior to cholesterol side-chain cleavage as PMA had no effect on the metabolism of 25-hydroxycholesterol to testosterone or 17 beta-estradiol. By comparison, A23187 had no effects on either dbcAMP- or 25-hydroxycholesterol-stimulated steroid production. Separation of vitellogenic and prematurational, full-grown (0.9-1.1 mm in diameter) ovarian follicles from the same fish lead to the demonstration of opposing actions of A23187 in the two follicle types. Whereas A23187 inhibited hCG-stimulated steroid production in vitellogenic follicles, it had an additive effect on the stimulatory action of hCG on testosterone production by prematurational, full-grown ovarian follicles. In conclusion, these studies on vitellogenic ovarian follicles demonstrate specific regulatory actions of calcium and protein kinase C at multiple steps in the steroidogenic cascade and that ovarian responsiveness to calcium changes during the course of follicle development in the goldfish.
Gen Comp Endocrinol 1994 Feb
PMID:Effects of activators of different intracellular signaling pathways on steroid production by goldfish vitellogenic ovarian follicles. 817 24

We evaluated the effects of two protein kinase C (PKC) inhibitors, staurosporine (ST) and H-7, on LH-activated phospholipase C and adenylate cyclase activity by measuring the production of inositol phosphates (IP) and cAMP in freshly dispersed granulosa cells from mature preovulatory follicles of laying hens. ST and H-7 dose-dependently potentiated LH-stimulated IP generation, whereas a protein kinase A (PKA) inhibitor (H-8) had no effect. The PKC activator, phorbol ester TPA (50 nM), significantly inhibited LH-stimulated IP production, which was completely prevented by ST. Both ST and H-7, while having no effect on basal cAMP levels, significantly and dose-dependently potentiated LH-stimulated, but not forskolin-stimulated cAMP production. However, progesterone production in response to LH, forskolin, and 8-Br-cAMP was inhibited in granulosa cells preincubated for 30 min with H-7 or ST. H-7 and ST had no effect on 25-hydroxycholesterol- and pregnenolone-supported progesterone production. These results support a negative feedback role for PKC in LH-initiated signal transduction in avian granulosa cells. PKC blockade removes the inhibitory effect on LH-stimulated phospholipase C and adenylate cyclase activity. The inhibitory effect of H-7 and ST on progesterone synthesis could be attributed to inhibition of PKA and/or steps proximal to cholesterol side-chain cleavage.
Gen Comp Endocrinol 1994 Mar
PMID:Signal transduction in avian granulosa cells: effects of protein kinase C inhibitors. 819 46

In Escherichia coli, adenylate cyclase activity is regulated by phosphorylated EnzymeIIA(Glc), a component of the phosphotransferase system for glucose transport. In strains deficient in EnzymeIIA(Glc), cAMP levels are very low. Adenylate cyclase containing the D414N substitution produces a low level of cAMP and it has been proposed that D414 may be involved in the process leading to activation by EnzymeIIA(Glc). In this work, spontaneous secondary mutants producing large amounts of cAMP in strains deficient in EnzymeIIA(Glc) were obtained. The secondary mutations were all deletions located in the cya gene around the D414N mutation, generating adenylate cyclases truncated at the carboxyl end. Among them, a 48 kDa protein (half the size of wild-type adenylate cyclase) was shown to produce ten times more cAMP than wild-type adenylate cyclase in strains deficient in EnzymeIIA(Glc). In addition, this protein was not regulated in strains grown on glucose and diauxic growth was abolished. This allowed the definition of a catalytic domain that is not regulated by the phosphotransferase system and produces levels of cAMP similar to that of regulated wild-type adenylate cyclase in wild-type strains grown in the absence of glucose. Further analysis allowed the characterization of the COOH-terminal regulatory domain, which is proposed to be inhibitory to the activity of the catalytic domain.
Mol Gen Genet 1994 May 25
PMID:The catalytic domain of Escherichia coli K-12 adenylate cyclase as revealed by deletion analysis of the cya gene. 820 86


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