Drugs online research references
Brain Res Mol Brain Res. 1994 Nov;27(1):145-51.
GABAA receptor stimulation enhances NMDA-induced Ca2+ influx in mouse cerebral cortical neurons in primary culture.
Ohkuma S, Chen DZ, Katsura M, Chen SH, Kuriyama K.
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
The effect of GABAA receptor stimulation on N-methyl-D-aspartate(NMDA)-induced [45Ca2+]influx has been examined using primary cultured cerebral cortical neurons. NMDA induced a dose-dependent increase in [45Ca2+]influx, which was blocked by MK-801 in a dose-dependent manner. GABAA receptor agonists significantly enhanced the NMDA-induced [45Ca2+]influx, and this enhancement was dose-dependently inhibited by bicuculline, although picrotoxin and tert-butyl-bicyclo[2.2.2]phosphoro-thionate (TBPS) exhibited no alterations in this stimulatory action of GABAA receptor agonists. Blockers of L-type voltage-dependent calcium channels significantly reduced the NMDA-induced [45Ca2+]influx. The increased [45Ca2+]influx by both NMDA and GABAA receptor agonists was also reduced by verapamil and nifedipine. These results suggest that the enhancement of NMDA-induced [45Ca2+]influx by GABAA receptor stimulation in immature cerebral cortical neurons may be due to the increased opening of voltage-dependent calcium channel by synergestic actions between NMDA and GABAA receptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7877444&dopt=Abstract
Am J Physiol. 1994 Aug;267(2 Pt 2):H804-11.
Smooth muscle cells affect endothelial membrane potential in rat aorta.
Marchenko SM, Sage SO.
Physiological Laboratory, University of Cambridge, United Kingdom.
The effects of vasoconstrictors on membrane potential of endothelium of intact rat aorta were investigated using the patch-clamp technique. Norepinephrine, endothelin (ET)-1, 5-hydroxytryptamine (5-HT), vasopressin, and angiotensin II evoked depolarization and oscillations in membrane potential. The alpha 1-adrenoreceptor agonist phenylephrine (PE), but not the alpha 2-agonist clonidine or the beta-agonist isoproterenol, evoked oscillations. The antagonist of 5-HT2-receptors, ketanserin, inhibited 5-HT-evoked oscillations. ET-3, unlike ET-1, did not evoke oscillations. The antagonists of voltage-operated Ca2+ channels, nifedipine and verapamil, inhibited vasoconstrictor-evoked oscillations, and the Ca2+ channel agonist BAY K 8644 enhanced oscillations. Acetylcholine and sodium nitroprusside inhibited PE-evoked oscillations. The inhibitors of NO synthase, N omega-nitro-L-arginine and NG-methyl-L-arginine, as well as methylene blue, enhanced oscillations. The intima of rat aorta with endothelium was removed from underlying smooth muscle. In this preparation, acetylcholine evoked a response similar to that in the intact vessel, but PE and ET-1 were without effect. These data suggest that vasoconstrictors acting on receptors on aortic smooth muscle evoke a response that is transferred to the endothelium and evokes depolarization and oscillations in endothelial membrane potential.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8067436&dopt=Abstract
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11748-52.
Human cytochrome P450 3A4: enzymatic properties of a purified recombinant fusion protein containing NADPH-P450 reductase.
Shet MS, Fisher CW, Holmans PL, Estabrook RW.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Human cytochrome P450 3A4 is recognized as the catalyst for the oxygen-dependent metabolism of a diverse group of medically important chemicals, including the immunosuppressive agent cyclosporin; macrolide antibiotics, such as erythromycin; drugs such as benzphetamine, nifedipine, and cocaine; and steroids; such as cortisol and testosterone to name but a few. We have engineered the cDNA for human cytochrome P450 3A4 by linkage to the cDNA for the rat or human flavoprotein, NADPH-P450 reductase (NADPH:ferrihemoprotein oxidoreductase, EC 1.6.2.4). An enzymatically active fusion protein (rF450[mHum3A4/mRatOR]L1) has been expressed at high levels in Escherichia coli and purified to homogeneity. Enzymatic studies show a requirement for lipid, detergent, and cytochrome b5 for the 6 beta-hydroxylation of steroids and the N-oxidation of nifedipine. In contrast, these additions are not required for the N-demethylation of erythromycin or benzphetamine. A spectrophotometrically detectable metabolite complex of P450 3A4 is formed during the metabolism of triacetyloleandomycin, and this has a pronounced inhibitory effect on the metabolism of both testosterone and erythromycin. These results relate to the interpretation of current methods used to assess the in vivo activity of P450 3A4.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8265621&dopt=Abstract
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