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

Changes in the EPSC and Ach-current amplitudes of Planorbis corneus LC-1 and RC-1 neurons has been comparatively investigated after the influence on their adenylate cyclase system in order to reveal postsynaptic mechanisms of the heterosynaptic facilitation. Both responses are n-cholinergic and depend on the membrane conductivity for Na+ and K+. Application of 5-HT has led to an increase of the EPSC and ACh current (in most cases) amplitudes by 100-300%. A negligible increase of the EPSC and at the same time a decrease of the Ach-current were observed in 30% of cells. It was, probably, a result of different contribution made by Na+ and K+ to the activation mechanism of the channel-receptor complex conductivity of the nonsynaptic cell membrane. Effects of 5-HT on EPSCs and Ach-current were imitated by actions of the phosphodiesterase blockers and adenylate cyclase activators. Both the blockers and activators depressed the EPSCs and Ach-current. Thus, activation of the adenylate cyclase system by serotonin has promoted development of the postsynaptic mechanisms of heterosynaptic facilitation in command neurons of Planorbis corneus.
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PMID:[Participation of the adenylate cyclase system in the postsynaptic mechanism of heterosynaptic facilitation]. 179 13

The effects of acetylethylcholine mustard (Aech-M) on the muscarinic receptor coupled adenylate cyclase system of intact GH3 cells were investigated. The concentration of Aech-M and Ach that inhibited specific [3H]N-methylscopolamine binding by 50% was similar for both compounds (9.3 microM for Ach and 10.7 microM for Aech-M). Pretreatment of intact GH3 cells or isolated membranes with 10 to 50 microM Aech-M, followed by washing, reduced the [3H]N-methylscopolamine binding capacity by 60% and 75-77%, respectively, without changing the KD value for the radioligand to the remaining receptors. Both Aech-M and Ach attenuated forskolin (1 microM) stimulated cAMP formation with half-maximal effects (EC50) occurring at 0.84 microM for Ach and 0.24 microM for Aech-M. The maximal inhibition was 70-80% for Ach and 30-40% for Aech-M. However, the dose-response for Aech-M was biphasic such that at high concentrations (greater than 50 microM) there was a reduction in its ability to attenuate cAMP formation. After 3 min incubation with either Ach or Aech-M, the addition of atropine completely reversed their inhibitory effect even though with Aech-M there was a greater than 50% reduction in receptor capacity. Furthermore, over a 12-min incubation, Ach produced a relatively stable 67-76% reduction in cAMP accumulation, whereas with Aech-M the initial attenuation was gradually reduced such that by 10 min of incubation, no effect was observed. Finally, pretreatment with Aech-M resulted in a reduced sensitivity to the action of Ach as the EC50 values for inhibition of cAMP accumulation were increased 7.6- and 13.5-fold, respectively, with little or no change in the maximal response. The data indicate that Aech-M produces a transient agonist effect to attenuate cAMP formation in intact GH3 cells followed by an antagonist action probably after irreversible binding to the receptor.
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PMID:Effect of acetylethylcholine mustard on muscarinic receptor-coupled attenuation of cAMP formation in intact GH3 cells. 216 88

1. The involvement of second messengers and of other chemical mediators, in the modulation of the membrane potential of the Schwann cell of the giant nerve fiber of the Tropical squid Sepioteuthis sepioidea is described. 2. The involvement of the cyclic nucleotide adenosine 3', 5' monophosphate (cAMP) in mediating the actions of the nicotinic Ach receptors of the Schwann cells is suggested. 3. The presence of octopaminergic receptors in the Schwann cells, mediating their actions through the activation of adenylate cyclase, is also described. 3. Receptors for vasoactive intestinal peptide (VIP) are also present on the Schwann cells, and their actions are mediated via a second messenger system that does not involve the activation of adenylate cyclase. 5. The three independent receptor systems referred above are able to interact in a complex way, which involves both their direct actions on the Schwann cell membrane potential and modulatory effects between the systems.
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PMID:Modulation of the membrane potential of the Schwann cell of the squid giant nerve fiber. 284 30

Our laboratory has recently been involved in investigating factors which influence plasticity of neurotransmitter phenotypic expression both in vivo and in culture. Our previous studies have shown that precursor neuroblasts are pluripotential with respect to neurotransmitter phenotype and respond differentially to microenvironmental signals. In the present study, we examined phenotypic expression in neuroblastoma cells, P2 clone, using the activities of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) as neuronal markers for the cholinergic and catecholaminergic phenotypes, respectively. Cells were plated and grown for 4 days in culture, harvested and frozen for assay of ChAT and TH. Basal activity of ChAT was 2.47 +/- 0.22 nmoles Ach formed /h/mg protein and that of TH was 5.23 +/- 0.41 pmoles CO2 formed /h/mg protein in control cultures. When intracellular cAMP levels were increased by addition to the growth medium of 10 micrograms/ml prostaglandin E1 (PGE1; a receptor-mediated enhancer of adenylate cyclase activity) or 200 micrograms/ml RO20-1724 (an inhibitor of cyclic nucleotide phosphodiesterase) the activity of TH was increased 340- and 423-fold, respectively. In marked contrast, the activity of ChAT was not affected by either agent. Double staining immunocytochemical examination demonstrated that both ChAT and TH were colocalized in the same cell. The molecular mechanism whereby catecholaminergic expression exclusively is affected in this cell model is currently under investigation. We conclude that (1) P2 neuroblastoma is a pluripotential cell line, (2) phenotypic expression in a homogenous cell population, such as P2 neuroblastoma, is differentially regulated. Moreover, this cell line is a unique model for studying the molecular mechanisms of phenotypic expression and neuronal plasticity.
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PMID:Differential regulation of phenotypic expression in a pluripotential neuroblastoma cell line. 792 54

To elucidate the effect of an opioid on airway smooth muscle relaxant responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of the opioid mu-receptor-specific agonist DAMGO (10(-5) M) or Tyr-D-Arg-phe-Lys-NH2 (10(-5) M) did not alter the resting tension or the contractile responses to Ach but augmented the relaxation induced by isoproterenol: the concentrations of isoproterenol required to produce a half-maximal effect were decreased from 1.9 +/- 0.6 x 10(-6) to 3.1 +/- 1.0 x 10(-7) M (P < .01) by DAMGO and from 2.1 +/- 0.4 x 10(-6) M to 4.3 +/- 0.7 x 10(-7) M (P < .01), by Tyr-D-Arg-phe-Lys-NH2. This effect of DAMGO was concentration-dependent and was abolished by naloxone or Cys2, Tyr3, Orn5, Pen7-amide, a mu-receptor antagonist. DAMGO likewise caused a leftward displacement of concentration-response curves for forskolin but was without effect on those for 3-isobutyl-3-methylxanthine and 8-bromo-cAMP. Also, DAMGO did not affect the relaxant responses to verapamil, nitroprusside or 8-bromo-cGMP. Incubation of bronchial smooth muscle with DAMGO (10(-5) M) potentiated the intracellular accumulation of cAMP induced by isoproterenol (10(-6) M) from 258 +/- 22 pmol/g tissue wt. to 420 +/- 27 pmol/g tissue wt. (P < .01), an effect that was abolished by naloxone. These results suggest that stimulation of opioid mu-receptors specifically augments beta adrenoceptor-mediated bronchodilation probably by acting at the site proximal to adenylate cyclase in the cAMP-dependent pathway.
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PMID:Stimulation of opioid mu-receptors potentiates beta adrenoceptor-mediated relaxation of canine airway smooth muscle. 853 Oct 94