Evidence from guinea-pig trachealis that Uptake2 of isoprenaline is enhanced by hyperpolarization of the smooth muscle.
Previous studies (Bönisch et al. 1985; Trendelenburg 1986, 1987) have provided evidence that Uptake2 of catecholamines is inhibited by depolarization of cells. The aim of this study was to further examine the relationship between Uptake2 and membrane potential by testing the hypothesis that Uptake2 is, conversely, stimulated by hyperpolarization of cells. The effects of beta-adrenoceptor agonists (isoprenaline and salbutamol) and beta-adrenoceptor antagonists (propranolol and ICI 118,551) on Uptake2 of isoprenaline were examined in guinea-pig trachealis muscle, in which stimulation of beta-adrenoceptors mediates hyperpolarization of the smooth muscle cells (Allen et al. 1985), and in rat heart, in which beta-adrenoceptor agonists do not cause hyperpolarization. In guinea-pig trachealis muscle segments, propranolol and ICI 118,551 reduced Uptake2 (as measured by the steady-state rate of corticosterone-sensitive formation of 3-O-methylisoprenaline normalized for the isoprenaline concentration) in tissues incubated in 2.5-250 nmol/l 3H-isoprenaline (in the range over which isoprenaline causes hyperpolarization of the muscle), but not in 1 nmol/l 3H-isoprenaline (which does not hyperpolarize the muscle). The normalized rates were greater in tissues incubated in 25 nmol/l than 1 nmol/l isoprenaline, and were enhanced by 2.5 mumol/l salbutamol in tissues incubated in 1 nmol/l isoprenaline. In rat hearts perfused with 1 or 25 nmol/l 3H-isoprenaline and U-0521 to inhibit catechol-O-methyltransferase, the rate of Uptake2 of isoprenaline, normalized for the isoprenaline concentration, was unaffected by the isoprenaline concentration or the presence of propranolol, ICI 118,551 or salbutamol.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
L J
LJ
Bryan-Lluka
H E
HE
Vuocolo
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007545:Isoproterenol