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 present studies were undertaken to explore the mechanism by which, as previous studies have shown, freeze-dried aqueous extracts (FDE) of plants of the species Lycopus virginicus and Lycopus europaeus, Melissa officinalis (Laminaceae), and Lithospermum officinale (Boraginaceae) have the ability to inhibit at least many of the effects of exogenous and endogenous TSH on the thyroid gland. To this end, we have examined the in vitro effects of FDE from these plants on the ability of bovine TSH (bTSH) to both bind to human thyroid plasma membranes (TPM) and activate adenylate cyclase therein. FDE of these four species produced a dose-related, ultimately complete, inhibition of the binding of 125I-labeled bTSH when studied at 4 C in a 20 mM Tris-HCl-0.5% BSA buffer, pH 7.45. Half-maximum inhibition of bTSH binding was produced by approximately 50 mU/ml bTSH and only about 10-30 micrograms/ml of the four active FDE. When studied in Tris-BSA-50 mM NaCl buffer at 37 C, these FDE remained inhibitory to bTSH binding, but their potency was decreased to about one fifth of that seen in the absence of NaCl. The binding of [125I]hCG to rat testis membranes was also inhibited by all of these FDE, but no effect on the binding of [125I]insulin to crude rat liver membranes was observed. In concentrations as high as 1 mg/ml, FDE of Verbena officinalis (Verbenaceae), which belongs to the same order (Tubiflorae) as the other plants, but exhibits no antithyrotropic or antigonadotropic activity in vivo, had no effect on either the binding of bTSH to thyroid membranes or the binding of hCG to rat testis membranes. No inhibition of [125I]bTSH binding occurred when TPM were preincubated with the four active FDE, washed, and then incubated with [125I]bTSH in medium devoid of FDE. Hence, the inhibition of [125I]bTSH binding seen when labeled hormone and active FDE were added together was not due to irreversible binding of FDE to TPM or damage to the TSH receptor. When [125I]bTSH was incubated with the active FDE in Tris-BSA and the mixture was chromatographed on Sephadex G-100 using the same buffer, [125I]bTSH was shifted from an apparent mol wt of 30,000 and eluted at the void volume. Direct binding of [125I]bTSH in fractions from the new, large molecular peak was nil. Addition of a large excess of unlabeled bTSH during preincubation prevented the shift in the elution pattern of [125I] bTSH produced by these FDE.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. 674 67

Mice that received five daily injection of methylphenidate HCl, 10-75 mg/kg, showed an increased running response to methylphenidate, cocaine, and amphetamine. Sensitization to methylphenidate persisted for at least 50 days. Repeated IP injections of methylphenidate into mice with unilateral striatal lesions increased ipsilateral turning in response to methylphenidate, but decreased contralateral turning after apomorphine. The climbing response to apomorphine in intact, methylphenidate-sensitized mice was also decreased. There was no change in either basal or dopamine-stimulated adenyl cyclase activity in the striata of sensitized mice, but there was a 36% increase in the specific binding of haloperidol. The rate of turnover of striatal dopamine was increased in sensitized mice. These results suggest that pretreatment with methylphenidate may alter the sensitivity of presynaptic dopamine receptors.
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PMID:Sensitization of mice to methylphenidate. 681 16

Sulpiride (100 mg IM), an atypical neuroleptic, which does not block dopamine (DA) receptors that are linked to adenylate cyclase, abolished the growth hormone (GH) response to the DA receptor agonist, apomorphine (Apo) HCl (0.5 mg SC) in seven healthy male subjects. These results suggest that Apo increases GH secretion in man by an effect on DA receptors that are not linked to adenylate cyclase.
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PMID:Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion. 713 55

A single-step chromatography on Matrex-Gel Blue A has been employed to obtain soluble extracts containing some of the most important antigens of Bordetella pertussis, pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (69-kDa outer membrane protein), fimbriae (FIM2 and FIM3) and adenylate cyclase (AC). Two supernatants, P19 (48.8 mg PT, 6.8 mg FHA, 17.3 mg AC, 13 mg FIM2 and 4.9 mg FIM3 per liter) and P21 (0.1 mg PT, 0.07 mg FHA, 0.46 mg FIM2 and 0.94 mg FIM3 per liter), resulting from bacteria grown in Stainer-Scholte medium, were submitted to chromatography. Fractions with the antigens were obtained after stepwise elution with 60 mM sodium phosphate buffer, pH 6.0; 50 mM Tris-HCl, pH 7.4; 50 mM Tris-HCl, pH 7.4/0.75 M MgCl2; 50 mM Tris-HCl, pH 7.4/4 M MgCl2 and 4 M urea. Preparations from P19 (containing 4.05 micrograms PT, 8.14 micrograms FHA, 6.3 micrograms AC, 3.37 micrograms 69-kDa, 9.54 micrograms FIM2 and 2.23 micrograms FIM3) and from P21 (with 0.175 micrograms PT, 0.28 micrograms FHA, 0.002 micrograms 69-kDa, 0.005 micrograms FIM2 and 0.122 micrograms FIM3) were detoxified with glutaraldehyde and tested as an acellular pertussis vaccine. These products were non-toxic for mice and induced high levels of antibodies against purified pertussis antigens, as judged by ELISA.
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PMID:A Bordetella pertussis acellular vaccine candidate: antigenic characterization and antibody induction. 754 83

Guinea pigs were infused with the beta-adrenoceptor agonist isoproterenol (400 micrograms/kg/hr, 7 days) and cardiac adenylate cyclase was detected using [3H]forskolin. Two populations of [3H]forskolin binding sites were present in heart, the affinities (KD 2 nM and 280 nM) and densities (Bmax 9 and 900 fmol/mg protein) of which were unchanged by isoproterenol infusion compared with vehicle (1 mM HCl). The autoradiographic localisation of [3H]forskolin binding was also unchanged. The G protein activators NaF 10 mM and 5'-guanylylimidodiphosphate (Gpp(NH)p) 10 microM increased [3H]forskolin binding in heart from vehicle-treated animals by 100% and 80% respectively. NaF-stimulated binding was unchanged in isoproterenol-treated animals, however, Gpp(NH)p-stimulated binding was reduced by 35% which may indicate an increased influence of Gi.
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PMID:[3H]forskolin binding to cardiac adenylate cyclase in guinea pigs chronically infused with isoproterenol. 765 11

The adenylate cyclase system has been implicated in taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alter taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to bitter, sweet, salty, sour, and glutamate tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryl-adenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The tast compounds tested were: NaCl (30 mM), monosodium glutamate-MSG (50 mM), sucrose (30 mM), HCl (5 mM and 10 mM), KCl (300 mM), quinine HCl (30 mM), MgCl2 (30 mM), erythromycin (0.7 mM and 1 mM), HCl (5 mM and 10 mM), and urea (2 M). The main findings were as follows. NaF (20 mM) significantly inhibited responses to bitter compounds up to 35% and enhanced the response to sucrose by 30%. NaCl (20 mM), used as a control for NaF, inhibited most responses up to 78% with no enhancement of sucrose as seen with NaF. 8BrcAMP (1.16 mM) reduced the responses to bitter-tasting quinine HCl, MgCl2, and erythromycin but not to urea.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulators of the adenylate cyclase system can alter electrophysiological taste responses in gerbil. 797 5

SR 57746A, 4-(3-trifluoromethylphenyl)-N-[2-(naphth-2-yl)ethyl]-1,2,3,6- tetrahydropyridine HCl, was studied for its specific 5-HT1A receptor agonist action and antidepressant-like effects in the rat. The compound showed a high affinity for 5-HT1A specific binding sites in the rat hippocampus (IC50 3 nM), moderate affinity (10(-7)-10(-6) M) for dopamine D2 receptor, 5-HT uptake, 5-HT2 and alpha 1-adrenoceptor binding sites and practically no effect on binding sites of monoamine, GABAA, benzodiazepine and histamine receptors. It inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes at concentrations of 10(-6) and 10(-5) M. The effect of 10(-6) M SR 57746A on forskolin-stimulated adenylate cyclase activity was completely antagonized by 10(-6) M (-)-propranolol. Administered per os as a three-dose course to rats, SR 57746A significantly increased struggling in the forced swimming test at doses from 0.3 to 3 mg/kg. Single doses had no such effect. The effect of a three-dose course with 1 mg/kg SR 57746A on rats' struggling was antagonized by pretreatment with 5 mg/kg i.p. metergoline, a non-selective 5-HT receptor antagonist, and by 20 mg/kg i.p. (-)-propranolol, an antagonist at 5-HT1 receptors. Three oral doses of 100 mg/kg parachlorophenylalanine, an inhibitor of 5-HT synthesis, and 100 mg/kg i.p. (+/-)-sulpiride, an antagonist at dopamine D2 receptors, also antagonized the effect of SR 57746A in the forced swimming test. The results show that SR 57746A has selectivity and high affinity for 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential antidepressant properties of SR 57746A, a novel compound with selectivity and high affinity for 5-HT1A receptors. 801 40

We have investigated the presence of high affinity LH/hCG-binding sites (RLH) in crude membranes from early pregnant rats uteri. The uterine concentration of available RLH increased from day 1 to day 3 (1.3 +/- 0.2 vs. 2.8 +/- 0.4 fmol/mg protein) without a change in the affinity constant (approximately 5 x 10(10) M-1). However, unoccupied uterine RLH disappeared in the periimplantation period (days 4-6). To determine if the drop in available RLH was consecutive to their occupancy, uterine membranes were treated with acidified medium (25 mM Tris-HCl, and 5 mM MgCl2, pH 2.5) to remove endogenous ligand. The number and affinity of total (occupied plus available) RLH in acid-eluted membranes were estimated by Scatchard analysis of [125I]hCG binding and compared with those of available RLH in untreated membranes from the same uterine preparation. The uterine concentration of total RLH increased first between days 1 and 2 (2.2 +/- 0.5 vs. 4.2 +/- 0.8 fmol/mg protein), then between days 3 and 4 (4.2 +/- 0.6 vs. 6.5 +/- 0.8 fmol/mg protein), before plateauing until day 6. Thus, the reduction in the available uterine RLH in the periimplantation period is largely due to occupancy, rather than down-regulation, of RLH. The occupancy of uterine RLH 1) increased during early pregnancy (day 1, approximately 20%; days 2-3, approximately 40%; days 4-6, approximately 100%), 2) paralleled the increase in total RLH number, and 3) was probably due to pituitary LH only. However, the blastocyst itself seemed to influence uterine RLH occupancy, since available uterine RLH were detected on day 5 of pseudopregnancy. The increase in total uterine RLH as well as the perfect synchrony between their occupancy and the previously described pattern of uterine cAMP concentration during rat early pregnancy suggest that the response of uterine (and more precisely luminal epithelium) adenylate cyclase to LH (and/or related substance originating from embryo) may determine uterine receptivity for ovoimplantation and subsequent decidualization.
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PMID:Uterine luteinizing hormone/human chorionic gonadotropin-binding sites in the early pregnant rat uterus: evidence for total occupancy in the periimplantation period. 844 Jan 85

The present study characterizes the neurochemical profile of the newly synthesized compound 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-be nzodioxole HCl (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (Ki: 0.35 nM) and moderate affinity for alpha 1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotransmitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.
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PMID:Novel benzodioxan derivative, 5-(3-[((2S)-1,4-benzodioxan-2- ylmethyl)amino]propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotonin1A receptors. 878 39

The intracellular signaling pathways responsible for tumor necrosis factor (TNF)-alpha stimulation of lymphocyte adhesion to brain microvascular endothelial cells (BMEC) were studied using inhibitors of protein kinase C (bisindolylmaleimide HCl, H-7, or staurosporine), or protein tyrosine kinase (genistein). Each of these blocked the ability of BMEC to respond to TNF-alpha. In contrast, BMEC treated with H-89, an inhibitor of protein kinase A, or the adenylate cyclase inhibitor, dideoxyadenosine, responded normally to TNF-alpha. Forskolin, an adenylate cyclase agonist, significantly increased lymphocyte adhesion to BMEC. These data indicate that intracellular signaling by TNF-alpha in BMEC is mediated through a protein kinase C and tyrosine kinase dependent pathway.
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PMID:Intracellular signaling of tumor necrosis factor-alpha in brain microvascular endothelial cells is mediated by a protein tyrosine kinase and protein kinase C-dependent pathway. 889 28


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