Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of adrenergic stimulation to the proarrhythmic effects of pinacidil (30 microM), an opener of ATP-sensitive potassium channels (K+ATP), was tested in an isolated guinea-pig heart model of global ischemia (10 min) and reperfusion (10 min). None (0%) of the control hearts (n=10) elicited arrhythmias during ischemia or reperfusion. In the pinacidil-treated group, one heart (5%) experienced episodes of ventricular tachycardia (VT)/fibrillation (VF) during normoxia. During ischemia, 63% (12 out of 19) of pinacidil-treated hearts exhibited episodes of VT or VF. Hearts not in VT or VF (n=7) at the time of reperfusion, exhibited 71% VT and 43% VT/VF upon reperfusion. Proarrhythmic effects of pinacidil during ischemia or reperfusion were completely reversed by glyburide (n=9; 10 microM), a K+ATP antagonist, or nadolol (n=9; 3 microM), a beta-adrenergic antagonist. Isoproterenol (n=10; 50 nM), a beta-adrenergic agonist, induced a 20% incidence of ischemic VT and VF, and a 70% incidence of reperfusion VF, while methoxamine (n=10; 10 microM), an alpha-adrenergic agonist, demonstrated little proarrhythmia (20% VT/VF at reperfusion only). Proarrhythmic effects of isoproterenol were reversed by nadolol, but not glyburide. Pinacidil caused a slight potentiation of tachycardia induced by a bolus injection of tyramine (30 micro g), an indirectly acting sympathomimetic, but bolus injections of pinacidil (100 micro g) had no effect on heart rate. Nisoxetine, a catecholamine uptake 1 inhibitor, had no proarrhythmic effects when given alone. Catecholamine levels were reduced in pinacidil-treated hearts relative to vehicle-treated. In conclusion, it is suggested that the proarrhythmic effects of pinacidil following global ischemia and reperfusion in the isolated perfused guinea-pig heart appears to involve stimulation of beta-adrenoceptors. These proarrhythmic effects of pinacidil do not appear to be mediated solely through direct opening of K+ATP, but rather through an indirect enhancement of catecholamine release.
J Mol Cell Cardiol 1998 Feb
PMID:Proarrhythmic effects of pinacidil are partially mediated through enhancement of catecholamine release in isolated perfused guinea-pig hearts. 951 18

Cocaine binds to dopamine (DA), serotonin (5-HT) and norepinephrine (NE) transporters blocking the reuptake of these monoamines into presynaptic terminals. As previously reported, continuous infusion of cocaine for seven days or GBR 12909, a selective dopamine uptake inhibitor, produced significant decreases in prodynorphin (PDYN) gene expression in the hypothalamus. Cocaine also produced a significant increase in PDYN mRNA in the caudate putamen, whereas GBR12909 has no effect and the selective serotonin uptake inhibitor fluoxetine decreases PDYN mRNA in the same brain region. The effect of the selective norepinephrine uptake inhibitor nisoxetine was examined on PDYN gene expression. Nisoxetine or vehicle was infused continuously for 7 days via osmotic minipump into male rats. This treatment produced significant increases in PDYN gene expression in the hypothalamus (183% of control), nucleus accumbens (142% of control) and hippocampus (124% of control) and a significant decrease in the caudate putamen (69% of control). These data suggest that nisoxetine affects PDYN gene expression and support a role for NE in the mechanisms underlying the effects of chronic exposure to psychoactive drugs. Moreover, nisoxetine, as well as fluoxetine, decreases PDYN mRNA in the caudate putamen, in contrast to the up-regulation produced by cocaine. Thus, the inhibition of NE uptake alone cannot account for the cocaine-induced increase of PDYN gene expression. These findings suggest that PDYN gene expression regulation by cocaine in the caudate putamen might be due to a combination of effects on two or three monoamine transporters, or to a mechanism unrelated to transporters inhibition.
Brain Res Mol Brain Res 2004 Aug 23
PMID:Effects of the selective norepinephrine uptake inhibitor nisoxetine on prodynorphin gene expression in rat CNS. 1530 27

Experimental data suggest that halothane anesthesia is associated with significant changes in dopamine (DA) concentration in some brain regions but the mechanism of this effect is not well known. Rat brain cortical slices were labeled with [(3)H]DA to further characterize the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [(3)H]DA that was dependent on incubation time and anesthetic concentration (0.012, 0.024, 0.048, 0.072 and 0.096 mM). This effect was independent of extracellular or intracellular calcium. In addition, [(3)H]DA release evoked by halothane was not affected by TTX (blocker of voltage-dependent Na(+) channels) or reserpine (a blocker of vesicular monoamine transporter). These data suggest that [(3)H]DA release induced by halothane is non-vesicular and would be mediated by the dopamine transporter (DAT) and norepinephrine transporter (NET). GBR 12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]DA evoked by halothane. Nisoxetine, a blocker of NET, reduced the release of [(3)H]DA induced by halothane. In addition, GBR 12909, nisoxetine and, halothane decrease the uptake of [(3)H]DA into rat brain cortical slices. A decrease on halothane-induced release of [(3)H]DA was also observed when the brain cortical slices were incubated at low temperature and low extracellular sodium, which are known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which induces DA release through reverse transport, decreased [(3)H]DA release induced by halothane. It is suggested that halothane increases [(3)H]DA release in brain cortical slices that is mediated by DAT and NET present in the plasma membrane.
Cell Mol Neurobiol 2007 Sep
PMID:Halothane increases non-vesicular [(3)H]dopamine release from brain cortical slices. 1768 Mar 57