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)

It has been found that TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), in rats, endoperitoneally or orally administered at dose of 1-10 mcg/kg, provokes irritability, aggressivity and restlessness (increase of spontaneous crossings in the shuttle box). The TCDD does not modify the conditioned avoidance (C.A.) or the conflictual situation. In "vitro" the TCDD stimulates directly the striatal and hypothalamic adenylate cyclase of rat. The TCDD increases the stimulation produced by dopamine on striatal adenylate cyclase. Haloperidol (dopamine antagonist) inhibits the stimulation produced by TCDD. TCDD does not significantly modify the stimulation by hystamine on hypothalamic adenylate cyclase. Cimetidine (H2) antagonist) causes a remarkable increase of the TCDD stimulating effect.
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PMID:[Neuropsychopharmacological effects of TCDD]. 74 17

Taste discs were dissected from the tongue of R. ridibunda and their cells dissociated by a collagenase/low Ca/mechanical agitation protocol. The resulting cell suspension contained globular epithelial cells and, in smaller number, taste receptor cells. These were identified by staining properties and by their preserved apical process, the tip of which often remained attached to an epithelial (associated) cell. When the patch pipette contained 110 mM KCl and the cells were superfused with NaCl Ringer's during whole-cell recording, the mean zero-current potential of 22 taste receptor cells was -65.2 mV and the slope resistance 150 to 750 M omega. Pulse-depolarization from a holding voltage of -80 mV activated a transient TTX-blockable inward Na current. Activation became noticeable at -25 mV and was half-maximal at -8 mV. Steady-state inactivation was half-maximal at -67 mV and complete at -50 mV. Peak Na current averaged -0.5 nA/cell. The Ca-ionophore A23187 shifted the activation and inactivation curve to more negative voltages. Similar shifts occurred when the pipette Ca was raised. External Ni (5 mM) shifted the activation curve towards positive voltages by 10 mV. Pulse depolarization also activated outward K currents. Activation was slower than that of Na current and inactivation slower still. External TEA (7.5 mM) and 4-amino-pyridine (1 mM) did not block, but 5 mM Ba blocked the K currents. K-tail currents were seen on termination of depolarizing voltage pulses. A23187 shifted the IK(V)-curve to more negative voltages. Action potentials were recorded when passing pulses of depolarizing outward current. Of the frog gustatory stimulants, 10 mM Ca caused a reversible 5- to 10-mV depolarization in the current-clamp mode. Quinine (0.1 mM, bitter) produced a reversible depolarization accompanied by a full block of Na current and, with slower time-course, a partial block of K currents. Cyclic AMP (5 mM in the external solution or 0.5 microM in the pipette) caused reversible depolarization (to -40 to -20 mV) due to partial blockage of K currents, but only if ATP was added to the pipette solution. Similar responses were elicited by stimulating the adenylate cyclase with forskolin. Blockage of cAMP-phosphodiesterase enhanced the response to cAMP. These results suggest that cAMP may be one of the cytosolic messengers in taste receptor cells. Replacement of ATP by AMP-PNP in the pipette abolished the depolarizing response to cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Patch-clamp study of isolated taste receptor cells of the frog. 244 95

This study was conducted to further characterize the previously described phenomenon of growth inhibition of neoplastically transformed C3H/10T1/2 cells (T10T1/2) by nontransformed C3H/10T1/2 clone 8 mouse embryo fibroblast (10T1/2) cells in the presence of inhibitors of cyclic adenosine 3':5'-monophosphate (cAMP) phosphodiesterase. The cAMP phosphodiesterase inhibitor dl-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO20-1724) was shown to be completely nontoxic to T10T1/2 cells at 10(-4) M, yet when added to mixed cultures of T10T1/2 cells and postconfluence growth-arrested 10T1/2 cells, colony formation and [3H]thymidine incorporation into T10T1/2 cells were virtually eliminated. This effect was dose dependent and was reversible upon drug withdrawal. In 10T1/2 cells, RO20-1724 caused a dose-dependent increase in cAMP levels from about 5 to 150 pmol/10(6) cells; in T10T1/2 cells, 10(-4) M drug treatment caused a 5-fold elevation in cAMP without a clear dose dependency. Cyclic guanosine 3':5'-monophosphate levels in 10T1/2 cells fell by 50% with drug treatment but were unmeasurable in T10T1/2 cells. When intracellular cyclic AMP levels were elevated by the adenyl cyclase stimulator forskolin, growth inhibition of T10T1/2 cells was again induced in mixed cultures but was not observed when added to T10T1/2 cells alone. Addition of RO20-1724 to low concentrations of forskolin produced a greater than additive effect on growth inhibition. Growth inhibition of T10T1/2 cells by RO20-1724 was shown to (a) require contact with, or extremely close proximity to, a confluent monolayer of 10T1/2 cells, (b) be maximum when seeded upon a growth-inhibited monolayer and not an actively growing 10T1/2 culture, and (c) not be decreased by continuous agitation of the culture medium, indicating that readily diffusible inhibitory factors are not involved. A model is presented whereby transformed cells can respond to but cannot themselves generate growth-inhibitory signals produced by post-confluence growth-inhibited nontransformed cells. The existence of these cellular interactions may well explain problems in the quantitation of transformed foci encountered in the use of this cell line as an assay system for chemical and physical carcinogens.
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PMID:Requirements for and kinetics of growth arrest of neoplastic cells by confluent 10T1/2 fibroblasts induced by a specific inhibitor of cyclic adenosine 3':5'-phosphodiesterase. 298 40

The benzamide derivative tiapride (Tiapridex, Synthelabo) has a highly selective antagonistic effect on striatal adenylate cyclase-independent dopamine-2 receptors. Its in vitro binding affinity is especially high for dopamine receptors which have been sensitized by pre-incubation with dopamine. The involvement of altered dopamine receptor sensitivity in several extrapyramidal dys- and hyperkinesia has been hypothesized. By its high affinity for these receptors, without any affinity for other neurotransmitter receptors of the brain, tiapride is especially well suited for the treatment of movement disorders related to functional dopamine hyperactivity. Even at higher doses, tiapride does not exceed a D2-receptor occupancy of 80%, which is in accordance with the finding that tiapride rarely causes acute extrapyramidal syndromes and has, up to now, never implicated in inducing tardive dyskinesias. On the contrary, clinical studies demonstrate its excellent efficacy in neuroleptic-induced tardive dyskinesia, L-Dopa-induced dyskinesias, psychomotor agitation in geriatric patients and choreatic movement disorders. Since tiapride is not available in the USA as yet, most of the studies concerning tiapride have been carried out in Europe. In a recent study, based on objective measurements, tiapride effectively controlled choreatic movements in patients suffering from Huntington's disease (HD). Tiapride is well tolerated in daily doses between 300 and 1200 mg. Adverse events are generally rare and mild.
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PMID:The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes. 1072 80