Presynaptic β‐adrenoceptors in rat atria: evidence for the presence of stereoselective β₁‐adrenoceptors

Abstract

1 Presynaptic fi-adrenoceptor activity was studied in rat isolated atria, previously loaded with[3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory #-adrenoceptor agonist. 2 Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked effiux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nm adrenaline. 3 The 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentrationdependent decrease in the activity of adrenaline. Cardioselective #-blocking drugs: acebutolol, betaxolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 > nebivolol > R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of a-adrenoceptors.4 The postsynaptic fi-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 > nebivolol > R 67 145.5 It is concluded that in rat isolated atria, presynaptic 2-and #1-adrenoceptors coexist and that facilitatory fl1-adrenoceptors are stereospecific.

Epinephrine and the genesis of hypertension.

“…18 -24 -26 -28^0 -32^6 - 46 Facilitative prejunctional ft-receptors have also been described. 47 " 49 Functionally, one could consider three potential roles for such receptors: as autoreceptors 50 activated by neuronally released norepinephrine, as "heteroreceptors" 50 activated by epinephrine, as a circulating hormone, or as autoreceptors stimulated by epinephrine transformed from a hormone to a neurotransmitter by its uptake and storage in sympathetic varicosities (Figure 1). There is little evidence that the neurotransmitter norepinephrine potentiates its own release.…”

Cardiovascular Effects of Intracerebroventricular Injections of (±)-Nebivolol and its Enantiomers—a Comparison with those of Metoprolol in the Rat

“…I). These three compounds have different PIadrenoceptor blocking potencies: (+)-nebivolol > ( f )-nebi-volol> (-)-nebivolol, as has been shown in-vitro and invivo (Pauwels et al 1988;Van de Water et al 1988a;Heimburger et al 1989). (f )-Nebivolol is a highly lipophilic compound devoid of intrinsic sympathomimetic activity (Janssens et al 1989).…”

Newer beta blockers and the treatment of hypertension

“…Improvement, rather than diminution, in cardiac performance is clearly desirable. More specific blockade of the aforementioned presynaptic effects on catecholamines, possibly via a receptor distinct from either the beta 1 or beta 2 receptor, opens exciting possibilities [17,18], but since the presynaptic receptor is probably beta2, then the lack of significant hypotensive effect of the selective beta 2 antagonist ICI 118551 suggest that further elaboration of this hypothesis is needed [19,20]. The pattern of blood lipids should either remain undisturbed or altered in a potentially beneficial way.…”