The adrenergic neuronal selectivity of 3H‐outflow elicited by electrical‐field stimulation of rabbit isolated pulmonary artery preloaded with 3H‐(‐)‐noradrenaline (3H‐NA) was examined. Following incubation (45 min) of arterial rings at 37°C with 3H‐NA (10‐6 M) and a 100 min wash‐out period, the sympathetic neurones were stimulated selectively and supramaximally, as regards tension development, with a constant current (250 mA; 300 monophasic pulses; 10 Hz; 0.3 ms). The initial stimulation‐induced 3H‐outflow was higher than the subsequent 5 outflows, which remained almost constant (39, 20, 19, 17, 16 and 16 pmol g‐1, respectively). 3H‐NA and 3H‐O‐methylated plus deaminated metabolites constituted 11% and 74%, respectively, of the total 3H‐outflow induced during the initial stimulation period, but 38% and 38%, respectively, during the second stimulation period. Omission of Ca2+ in the physiological salt solution reduced the 6 stimulation‐induced outflows to 67, 40, 35, 24, 21 and 21%, respectively, of the untreated preparations. Bretylium (3 × 10‐5 M) or tetrodotoxin (10‐6 M) reduced the 3H‐outflow to approximately the same extent. Stimulation‐induced outflows from artery rings preloaded with 3H‐NA in the presence of cocaine (10‐3 M) or in the cold (3°C) approximated the Ca2+, bretylium and tetrodotoxin‐insensitive release. These treatments all completely blocked the neurogenic contractile response. When artery rings were preloaded with 3H‐NA in the presence of normetanephrine (10‐4 M), the stimulation‐induced Ca2+‐insensitive outflows were markedly reduced. The results suggest that the field stimulation‐induced release of 3H‐NA is in part of extraneuronal origin.
Peripheral sympathetic nerve terminals in many tissues, but not all, are endowed with beta-adrenoceptors. Activation of these result in an enhancement of noradrenaline release evoked by electrical nerve stimulation. These so-called presynaptic beta-adrenoceptors are possibly located on the outer surface of the varicosity of the noradrenergic nerves. A postsynaptic location, however, is also a possibility. The presynaptic beta-adrenoceptors appear to be of the beta 2-adrenoceptor subtype. However, specific classification is lacking. The stereospecificity of the beta-adrenoceptors is controversial. These receptors are not activated by noradrenaline released from sympathetic nerves. Adrenaline derived from the adrenal medulla may be the physiological activator. Either circulating adrenaline or adrenaline taken up by sympathetic nerve terminals and then released as a cotransmitter with noradrenaline activates the presynaptic beta-adrenoceptors. In the latter case, a "positive" feedback" loop may be formed.
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