Modulation of uptake2 of 3H-(+/-)-isoprenaline by isoprenaline-induced depolarization of rat salivary gland cells.
Previous observations by Almgren and Jonason (1974) showed that propranolol is able to increase the extraneuronal accumulation of 3H-isoprenaline in rat salivary gland slices. The present experiments were carried out in order to test the hypothesis that 3H-isoprenaline, by acting on beta-adrenoceptors, might depolarize the gland cells and thereby hinder its own uptake2 and that this hindrance might be prevented by propranolol. After inhibition of catechol-O-methyltransferase the extraneuronal accumulation of the 3H-catecholamine in slices of rat salivary glands was determined subsequent to 20 min of exposure of the tissue to 0.5 to 5,000 nmol/l 3H-(+/-)-isoprenaline. Expressed as a tissue/medium ratio, accumulation decreased with increasing amine concentration, although all amine concentrations were well below those saturating uptake2. The 3H-isoprenaline-induced decrease of the tissue/medium ratio was antagonized by (-)-propranolol, and increasing concentrations of the antagonist were needed to antagonize the effect of increasing concentrations of 3H-isoprenaline. In parallel experiments K+-induced (60 mmol/l) depolarization reduced the tissue/medium ratio observed for 0.5 nmol/l 3H-(+/-)-isoprenaline. Gland slices were preloaded with 3H-(+/-)-isoprenaline and then washed out for 60 min with solution not containing labelled amine. When 500 nmol/l (+/-)-isoprenaline were present in the wash-out solution, the addition of 10 mumol/l (-)-propranolol impeded the efflux of 3H-isoprenaline. In parallel experiments, K+-induced (60 mmol/l) depolarization facilitated the efflux of 3H-isoprenaline [in the presence of 10 mumol/l (-)-propranolol]. The results support the working hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004347:Drug Interactions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009467:Neuromuscular Depolarizing Agents; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012469:Salivary Glands / Q000187:drug effects* / Q000294:innervation
D009467:Neuromuscular Depolarizing Agents; D012110:Reserpine; D011433:Propranolol; D007545:Isoproterenol; D011188:Potassium