Modulation of noradrenaline release by presynaptic alpha-2 and beta adrenoceptors in rat atria. Effect of pretreatment with clenbuterol.

The effect of pretreatment with the beta-2-selective adrenoceptor agonist, (+/-)-clenbuterol (0.3 mg/kg, twice daily, 14 days) on prejunctional alpha-2- and beta-adrenoceptors was studied in rat atria. When atria from non-pretreated rats had been preincubated with (3H)-noradrenaline, (-)-isoprenaline (0.02 to 4.0 microM) did not affect tritium overflow evoked by stimulation of the cardioaccelerant nerves, but a higher concentration (40 microM) decreased it. Blockade of prejunctional inhibitory alpha-2-adrenoceptors by yohimbine (0.03, 0.3 and 0.8 microM) enhanced the overflow of tritium. In the presence of yohimbine, isoprenaline (1.2 microM) significantly increased stimulation-induced transmitter overflow, suggesting that in rat atria the facilitatory effect of isoprenaline mediated via prejunctional beta-adrenoceptors, is masked by the dominant influence of inhibitory alpha-2-adrenoceptors. (-)-Propranolol (0.1 microM) prevented the isoprenaline-induced increase in atrial rate and the isoprenaline-induced enhancement of transmitter release in the presence of yohimbine (0.3 microM), but did not modify by itself the stimulation-induced efflux of tritium, suggesting that neuronally released noradrenaline failed to activate facilitatory prejunctional beta-adrenoceptors. When atria from clenbuterol-pretreated rats had been preincubated with 3H-noradrenaline, the facilitatory effect of yohimbine 0.03 and 0.3 microM was markedly enhanced and, in this case, isoprenaline (1.2 and 12.0 microM) failed to cause its facilitatory effect in the presence of the alpha-2-adrenoceptor antagonist. Propranolol did not modify the facilitatory effect of yohimbine. No changes in the isoprenaline-induced increase in atrial rate were observed in clenbuterol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)