The effects of (-)-cromakalim and glibenclamide on uptake2 in guinea-pig trachealis muscle.
In a recent study, we have shown that hyperpolarization of cells by beta-adrenoceptor agonists results in stimulation of the uptake2 process for catecholamines. The aim of the present study was to further explore the hypothesis that uptake2 is dependent on membrane potential by examining the effects of the K(+)-channel opening drug, (-)-cromakalim, and the K(+)-channel blocking drug, glibenclamide, on uptake2 of isoprenaline. The effects of these drugs were examined in guinea-pig trachealis muscle, in which isoprenaline and cromakalim cause hyperpolarization, and in rat heart, in which isoprenaline and cromakalim have little effect on membrane potential. In guinea-pig trachealis muscle segments, 1 mumol/l glibenclamide reduced uptake2 (as measured by the steady-state rate of corticosterone-sensitive formation of 3H-3-O-methylisoprenaline normalized for the isoprenaline concentration) in tissues incubated in concentrations of 3H-(+/-)-isoprenaline that hyperpolarize the muscle (25 and 250 nmol/l) but not at an isoprenaline concentration that did not hyperpolarize the muscle (1 nmol/l). (-)-Cromakalim (10 mumol/l), which hyperpolarizes the trachealis muscle, increased uptake2 of isoprenaline (1 or 25 nmol/l) and this effect of (-)-cromakalim was inhibited by glibenclamide. In rat hearts perfused with 1 or 25 nmol/l 3H-(+/-)-isoprenaline and 10 mumol/l U-0521 to inhibit catechol-O-methyltransferase, the rate of uptake2 of isoprenaline was unaffected by cromakalim or glibenclamide. The results show that hyperpolarization of cells by various mechanisms can result in stimulation of uptake2 of catecholamines and provide further evidence to support the hypothesis that the uptake2 transport process is driven by the membrane potential of cells.
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
L J
LJ
Bryan-Lluka
H E
HE
Vuocolo
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D007545:Isoproterenol / Q000493:pharmacokinetics; D008297:Male; D008564:Membrane Potentials; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D007545:Isoproterenol; D005905:Glyburide