β₂‐Adrenoceptors Facilitating Noradrenaline Secretion from Human Vasoconstrictor Nerves

Abstract

Isolated biopsy specimens of human peripheral arteries and veins, preincubated with 3H-(-)- noradrenaline (NA) to label the neural stores of NA, were used to study the Beta-adrenoceptors previously found to increase the secretion of 3H-NA evoked by electrical field stimulation of the adrenergic nerves of this tissue. The increase in nerve stimulation induced secretion of 3H-NA caused by 0.04 muM isoprenaline was prevented by 1 muM propranolol. This beta-blocking drug by itself slightly but significantly depressed the secretion of 3H-NA caused by nerve stimulation in the absence of isoprenaline. While the secretion of 3H-NA was not affected by known beta1-agonists, it was dose-dependently and reversibly increased by two different beta2-agonists. The effect of isoprenaline on 3H-NA secretion was not altered by a selective beta1-antagonist, but strongly reduced or abolished by a beta2-blocking drug. The results indicate that the beta-adrenoceptors involved in the control of NA secretion from the vasoconstrictor nerves of human omental blood vessels are only to a minimal extent stimulated by NA secreted from the nerves, and therefore do probably not mainly serve to mediate local positive feedback control of transmitter secretion; the receptors appear to be beta2 in nature.

Adrenaline Activation of Prejunctional Β‐adrenoceptors in Guinea‐pig Atria

“…The relatively selective fi2-adrenoceptor agonists, terbutaline and salbutamol, enhance transmitter release in human omental arteries and veins, whereas the fll-adrenoceptor agonist, H 110/38, does not (Stjarne & Brundin, 1976).…”

THE EFFECTS OF (+)‐ AND (–)‐PROPRANOLOL ON 3H‐TRANSMITTER EFFLUX IN GUINEA‐PIG ATRIA AND THE PRESYNAPTIC β‐ADRENOCEPTOR HYPOTHESIS

“…However, propranolol by itself did not decrease efflux, in contrast to the observation of these previous workers. Others have also described the inability of propranolol to reduce stimulation-induced efflux in various test preparations Starke et al, 1975;Stjarne & Brundin, 1976) and some have interpreted this as signifying a minor physiological role for presynaptic f-receptors under ordinary conditions of neuronal excitation.…”

“…The mean pD2 values in 13 tissues each for a-and P-mediated responses was 6.45 and 5.36, respectively. Although fl,-receptors have a greater affinity for noradrenaline than do #2-receptors, the presynaptic sites which interact with isoprenaline do not clearly fall into the former category (Dahloff, Ablad, Borg, Ek & Waldeck, 1975;Stjarne & Brundin, 1976). f2-Receptor agonists but not a fl-agonist enhanced transmitter efflux in human omental artery and vein preparations (Stjarne & Brundin, 1976).…”

An assessment of the partial agonist activity of Ro 31‐1118, flusoxolol and pindolol in man.

“…However in a study comparing the effects of atropine and salbutamol it was noted that with comparable increases in heart rate salbutamol increased cardiac output while atropine did not (Gibson & Coltart, 1970). Again, stimulation of presynaptic 132-adrenoceptors has been shown to release catecholamines from human vasoconstrictor nerves (Stjarne & Brundin, 1976) and this may have contributed to the rise in systolic blood pressure.…”

“…Salbutamol has been shown to increase supine heart rate in previous studies (Leitch et al, 1976;Philips et al, 1980;Kennedy & Simpson, 1969) and the specific 32-adrenoceptor antagonist, ICI 118,551 (Bilski et al, 1983) has been shown to abolish this increase in heart rate (McCaffrey et al, 1986) indicating that it is mediated by the 12-adrenoceptor. However the mechanism of the rise in heart rate is unclear and may be partly reflex, secondary to peripheral vasodilation or due to direct stimulation of P2-adrenoceptors in the heart (Stiles et al, 1983) or stimulation of presynaptic 132-adrenoceptors facilitating noradrenaline release at the sympathetic nerve endings (Stjarne & Brundin, 1976).…”