Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 direct effects of estradiol-17 beta (E2), diethylstilbestrol (DES) and tamoxifen on testicular testosterone production by purified immature pig Leydig cells in vitro were studied. Leydig cells were obtained from 3-4 weeks old piglet testes by enzymatical dispersion followed by discontinuous Percoll gradient centrifugation. Leydig cells were treated with E2, DES, and tamoxifen in the absence or presence of LH after 12 h of incubation. Media were collected 48 h later for testosterone and cAMP measurement. E2 did not affect basal testosterone production. When Leydig cells were incubated with increasing concentrations (0.001-10.0 micrograms/ml) of E2, DES, or tamoxifen for 48 h, LH-stimulated testosterone production was reduced. The degree of this reduction was dependent on E2, DES, and tamoxifen, and a concentration of E2 and DES and tamoxifen higher than 100 ng/ml and 10 ng/ml was needed, respectively. DES and tamoxifen also reduced LH-stimulated cAMP formation. When equal concentrations of DES and tamoxifen were added concomitantly to Leydig cells, the inhibition was additive, indicating that tamoxifen does not prevent the inhibitory effects of DES. Forskolin, an activator of adenylate cyclase, stimulated testosterone production to an extent comparable to that attained with LH, and DES and tamoxifen reduced forskolin-stimulated testosterone production. DES and tamoxifen suppressed the conversion of exogenous pregnenolone and progesterone to testosterone, but did not affect the conversion of 17 alpha-hydroxyprogesterone to testosterone, suggesting a specific inhibition of 17 alpha-hydroxylase. These results suggest that E2, DES, and tamoxifen directly inhibit immature pig Leydig cell steroidogenesis, at least in part via an inhibition of cAMP formation and a decrease in the activity of 17 alpha-hydroxylase.
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PMID:In vitro effects of estradiol, diethylstilbestrol and tamoxifen on testosterone production by purified pig Leydig cells. 166 95

The role of signal transduction systems was examined in the secretion of GH-releasing hormone (GHRH) and somatostatin (SS) from perifused rat hypothalamic fragments. Forskolin, an adenylate cyclase activator, stimulated the release of GHRH and SS in a concentration-dependent manner (10-100 microM) with greatest stimulation for GHRH at 100 microM (mean +/- SE, 249 +/- 14%) and for SS at 30 microM (172 +/- 18%). (Bu)2cAMP also augmented GHRH and SS release. The protein kinase-C activator phorbol 12-myristate 13-acetate did not significantly stimulate basal GHRH or SS release at concentrations of 10 nM to 1 microM. The calcium ionophore A23187 enhanced the release of GHRH and SS in a concentration-dependent manner (2-20 microM), with the greatest responses of 282 +/- 50% at 10 microM and 189 +/- 24% at 20 microM, respectively. Potentiation by phorbol 12-myristate 13-acetate of forskolin-stimulated GHRH and SS release was observed. A23187 at 10 microM did not enhance forskolin-stimulated GHRH release, but did potentiate forskolin-stimulated SS release in a more than additive response. We conclude that there is 1) cAMP stimulation of hypothalamic GHRH and SS release, 2) a modulating role of protein kinase-C on cAMP-stimulated release of GHRH and SS, 3) a stimulatory role of the calcium messenger system for GHRH and SS release, 4) interaction of the signal pathways with differences in net GHRH and SS responses, and 5) a modulatory effect of protein kinase-C in perifused hypothalamic fragments which differs from the stimulation of basal GHRH and SS release reported in fetal-derived hypothalamic cell cultures. Our observations suggest an important regulatory role of interacting signal transduction systems in the hypothalamic secretion of GHRH and SS.
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PMID:Signal transduction systems in growth hormone-releasing hormone and somatostatin release from perifused rat hypothalamic fragments. 167 98

The present report provides evidence for a novel function for the neuropeptide vasoactive intestinal peptide (VIP). We demonstrate that VIP increases the cholinergic and the noradrenergic properties of cultured chick sympathetic neurons without changing neuronal survival and metabolism. VIP induces a 10- to 15-fold increase in the activity of choline acetyltransferase and an approximately twofold increase in the activity of tyrosine hydroxylase. Forskolin, an activator of adenylate cyclase, mimics all the effects of VIP on these cells. In addition, the effects of forskolin and VIP at optimal concentrations are not additive. Furthermore, VIP induces a rapid increase in the intracellular cAMP levels. Thus VIP acts via a cAMP-dependent pathway to enhance the cholinergic and noradrenergic properties of cultured chick sympathetic neurons.
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PMID:The neuropeptide VIP modulates the neurotransmitter phenotype of cultured chick sympathetic neurons. 168 92

Catecholamines (CAs) had been used for the treatment of congestive heart failure (CHF). However, since continuous administration of CAs develops tolerance in hemodynamics presumably due to desensitization of beta-adrenergic receptor (beta AR)-adenylate cyclase (AC) system, beta antagonist, instead of beta agonist, has recently been employed to treat CHF, in that it may recover beta AR-AC system. In this study, the precise mechanisms of alterations in cardiac beta AM-AC system after chronic administration of beta agonist or antagonist, were investigated. The rats were treated continuously for 14 days with saline, isoproterenol (ISO), atenolol (ATENO), or denopamine (DENO), a new positive inotropic agent with beta 1 selective AR agonistic properties, which is reported to hardly cause the tolerance in clinical studies. beta AR density (Bmax) was markedly reduced by ISO and slightly increased by ATENO. Forskolin stimulated cyclase activity was reduced markedly by ISO. Total amount of the pertussis toxin substrates (inhibitory G-protein; Gi) and cholera toxin substrates (stimulatory G-protein; Gs) were not different among 4 groups. However, Gs activity measured by human platelet reconstitutive assay was reduced by ISO and DENO. These results indicate that ISO-induced desensitization in caused by the reduction in Gs and AC-catalytic activity as well as by the down-regulation of beta AR. Furthermore, it is suggested that DENO may cause slight desensitization of beta AR-AC system due to reduced Gs activity.
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PMID:[Isoproterenol, denopamine, and atenolol-induced alterations in beta-adrenergic receptor-adenylate cyclase system of rat myocardium]. 168 39

A role of D2-dopaminergic neurotransmission in the regulation of melatonin biosynthesis in retina was studied in vivo in chickens. The nighttime rise in serotonin N-acetyltransferase (NAT)--the penultimate and key regulatory melatonin-synthesizing enzyme--was potently inhibited by both acute light exposure and agonists of dopamine D2-receptor (quinpirole, bromocriptine, and apomorphine). Spiroperidol, a selective dopamine D2-receptor blocker, increased the enzyme activity in light-exposed chickens, but had no effect in animals kept in darkness. Inhibitors of cyclic nucleotide phosphodiesterase, aminophylline, and 3-isobutyl-1-methylxanthine given peripherally, along with a direct adenylate cyclase activator forskolin injected directly into the eye, mimicked the action of darkness, and markedly enhanced the retinal NAT activity when administered to animals maintained in an illuminated environment. Dopamine D2-receptor agonists had no effect on aminophylline-stimulated enzyme activity, whereas spiroperidol enhanced it. Forskolin-driven NAT activity was suppressed by quinpirole. Spiroperidol and aminophylline given alone at different times of day under light conditions stimulated NAT activity, and their effects were mainly additive when given in combination. SCH 23390, a selective D1-dopamine receptor antagonist, did not affect the rise in NAT activity of chicken retina produced by either darkness or by aminophylline. The results provide further evidence that dopamine, acting via D2-receptors, mediates the inhibitory effects of light on the cyclic AMP-dependent dark-evoked induction of NAT activity in chicken retina.
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PMID:Serotonin N-acetyltransferase activity in chicken retina: in vivo effects of phosphodiesterase inhibitors, forskolin, and drugs affecting dopamine receptors. 168 20

Treatment of quiescent MG-63 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) or platelet-derived growth factor (PDGF) stimulates the rapid accumulation of c-myc RNA. We have now determined that a similar effect can be induced by cAMP. Treatment with forskolin (an activator of adenylate cyclase), IBMX (a phosphodiesterase inhibitor), PGE1, and isoproterenol stimulated accumulation of both cAMP and c-myc RNA, but no increase in either cAMP or c-myc RNA was seen with the inactive forskolin analog 1,9-dideoxyforskolin. Forskolin and IBMX acted synergistically in stimulating accumulation of both cAMP and c-myc RNA. However, three lines of evidence indicated that PDGF action is not mediated by cAMP. First, PDGF treatment caused no elevation of cAMP within 1 h, even in the presence of IBMX. Second, the kinetics of c-myc RNA elevation after treatment with PDGF or forskolin were similar, ruling out delayed onset of cAMP stimulation. Finally, simultaneous treatment with forskolin and the calcium ionophore A23187 enhanced the elevation of c-myc RNA levels; no such effect was seen with PDGF. We had previously shown that PDGF action is not affected by prior treatment of MG-63 cells with TPA, a treatment which desensitizes the c-myc response to TPA. Similarly, TPA pretreatment had minimal effect on forskolin or IBMX-induced c-myc expression. These data suggest that cAMP, phorbol esters, and PDGF act independently to stimulate c-myc RNA expression in MG-63 cells. However, nuclear runoff experiments and RNA half-life measurements demonstrated that PDGF, phorbol ester, and cAMP all act to increase the transcription of the MYC gene.
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PMID:Platelet-derived growth factor-stimulated c-myc RNA accumulation in MG-63 human osteosarcoma cells is independent of both protein kinase A and protein kinase C. 168 64

The present investigation was undertaken to examine the possible role of cAMP in PTH-stimulated prostaglandin (PG) production in organ cultures of neonatal mouse parietal bones. Cultures were treated with PTH, forskolin, isobutylmethylxanthine (IBMX), and 8-bromo-cAMP (8BrcAMP). We found that similar concentrations of PTH stimulate cAMP formation and increase PG production in this culture system. Forskolin, a direct activator of adenylate cyclase, was also a potent stimulator of cAMP and PG production. The effect was dose dependent, with a maximum at 10(-5) M. The time courses for PTH- and forskolin-stimulated PG production were similar, and there was a close and similar correlation between cAMP production at 15 min and PGE2 production at 6 h for both agents. An increase in PG production was also observed when IBMX, which elevates cAMP levels in cells by inhibiting cAMP phosphodiesterase, or the cAMP analog 8BrcAMP was added to the cultures. In addition, IBMX enhanced the PGE2 responses to PTH, forskolin, and 8BrcAMP. These findings indicate that stimulation of PG production by PTH may be mediated by cAMP.
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PMID:Evidence that adenosine 3',5'-monophosphate mediates hormonal stimulation of prostaglandin production in cultured mouse parietal bones. 168 90

1. Bull-frog sympathetic neurones in primary culture were voltage clamped in the whole-cell configuration. The pipette solution contained ATP (5 mM). 2. A hyperpolarization-activated sodium-potassium current (H-current: IH) was separated from other membrane currents in a nominally calcium-free solution containing cobalt (2 mM), magnesium (4 mM), barium (2 mM), tetraethylammonium (20 mM), tetrodotoxin (3 microM), apamin (30 nM) and 4-aminopyridine (1 mM). IH was selectively blocked by caesium (10-300 microM). 3. The steady-state activation of IH occurred between -60 and -130 mV. The H-conductance was 4.1-6.6 nS at the half-activation voltage of -90 mV. With the concentrations of potassium and sodium ions in the superfusate at 20 and 70 mM, respectively, the reversal potential of IH was about -20 mV. IH was activated with a time constant of 2.8 s at -90 mV and 22 degrees C. The Q10 between 16 and 26 degrees C was 4.3. 4. A non-hydrolysable ATP analogue in the pipette solution did not support IH activation. Intracellular 'loading' of GTP-gamma-S (30-500 microM) led to a progressive activation of IH. 5. Forskolin (10 microM) increased the maximum conductance of IH by 70%. This was associated with a depolarizing shift in the half-activation voltage (5-10 mV) and in the voltage dependence of the activation/deactivation time constant of IH. 6. Essentially the same results as with forskolin were obtained by intracellular 'loading' with cyclic AMP (3-10 microM) or bath application of 8-bromo cyclic AMP (0.1-1 mM), dibutyryl cyclic AMP (1 mM) and 3-isobutyl-1-methylxanthine (0.1-1 mM). 7. The protein kinase inhibitor H-8 (1-10 microM) decreased the peak amplitude of IH. Phorbol 12-myristate 13-acetate (10 microM), a protein kinase C activator, was without effect. 8. It is concluded that a voltage-dependent cation current can be regulated by the basal activity of adenylate cyclase, presumably through protein kinase A, in vertebrate sympathetic neurones.
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PMID:Cyclic AMP regulates an inward rectifying sodium-potassium current in dissociated bull-frog sympathetic neurones. 169 Dec 92

Islet-activating protein was unilaterally microinjected into rat striatum, and a dialysis cannula was implanted into the same area under anesthesia. After 2 days, various agents were perfused continuously into the striatum through the dialysis membrane, under freely moving conditions. Islet-activating protein (2 micrograms/2 microliters) treatment alone did not change in vivo striatal dopamine (DA) release and metabolism, but completely abolished the increase of striatal DA release evoked in vivo by the M1-selective agonist McN-A-343 (10(-7) M). Forskolin (10(-5) M), an adenylate cyclase activator, increased DA release and showed an additive effect on the DA release evoked by McN-A-343. Polymyxin B, a rather selective inhibitor of protein kinase C, decreased DA release and completely blocked the effect of McN-A-343. These results suggest that in vivo striatal DA release elicited by M1 muscarinic receptors is coupled with interaction with a Go protein and is induced by activation of protein kinase C.
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PMID:In vivo striatal dopamine release by M1 muscarinic receptors is induced by activation of protein kinase C. 169 83

Endocochlear potential (EP) and cochlear microphonics (CM) were recorded during the perilymphatic perfusion with forskolin known as an adenylate cyclase stimulant. Forskolin produced a reversible EP elevation in a dose-dependent manner. Perfusion with 1,9-dideoxy-forskolin, an analogue of forskolin that does not stimulate adenylate cyclase, had no effect on EP, whereas perfusions with other agents that raise the cAMP-level (IBMX, a phosphodiesterase inhibitor, and dbcAMP) duplicated the effect of forskolin. The vigorous CM during the EP elevation and the large negative EP induced by anoxia superimposed on the elevated EP indicate that the K+ diffusion potential through the hair cell membrane cannot be altered by forskolin. The results suggest that the adenylate cyclase system in the stria vascularis and/or Reissner's membrane may modulate the generation of EP.
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PMID:Effects of forskolin and 1,9-dideoxy-forskolin on cochlear potentials. 169 40


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