Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery

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Abstract
A search was performed for presynaptic, release-modulating receptor systems on the postganglionic sympathetic nerves of rabbit pulmonary artery. Strips of the artery were preincubated with (-)-3H-noradrenaline and then superfused and stimulated transmurally. 1. Tetrodotoxin, guanethidine, and omission of calcium all suppressed the stimulation-evoked over-flow of tritium, thus confirming selective release from noradrenergic neurones. 49% of the stimulationevoked overflow of total tritium consisted of 3H-noradrenaline, 22% of 3H-3,4-dihydroxyphenylglycol (DOPEG), and 9% of 3H-normetanephrine. Cocaine virtually abolished the evoked overflow of 3H-DOPEG; further addition of corticosterone also abolished that of 3H-normetanephrine. In the presence of cocaine plus corticosterone, unmetabolized 3H-noradrenaline accounted for 86% of the stimulationevoked overflow of total tritium. The overflow evoked per pulse was 2.2×10−5 of the tritium content of the tissue (1 Hz); it increased 2-fold when the frequency was raised to 8 Hz. 2. Presynaptic α-adrenoceptors have previously been demonstrated in this tissue (Starke et al., 1975b). High concentrations of isoprenaline reduced the stimulation-evoked overflow of tritium, presumably by α-adrenergic inhibition. No presynaptic effect of up to 10−5 M normetanephrine and metanephrine was found. 3. Dopamine slightly diminished the stimulation-evoked overflow of tritium, but only at 100 times the inhibitory threshold concentration of noradrenaline (which is 10−8 M; Starke et al., 1975b), probably through activation of presynaptic α-adrenoceptors. Apomorphine failed to reduce the evoked overflow whether the superfusion medium contained cocaine and corticosterone or not. 4. Isoprenaline (10−9–10−6 M) did not change the evoked overflow whether the medium contained cocaine and corticosterone or not, and whether the frequency was 1 or 2 Hz. Propranolol also had no effect. 5. Angiotensin II increased the stimulation-evoked overflow both in the absence and in the presence of cocaine and corticosterone. Equieffective concentrations of angiotensin I were 10 times higher. Saralasin had no effect, whereas 1-Sar,8-Ile-angiotensin produced a small increase. Both of the latter peptides behaved as presynaptic antagonists of angiotensin II. A presynaptically supramaximal concentration of the α-adrenergic agonist oxymetazoline prevented the facilitatory action of yohimbine, but not that of angiotensin II. Separation of 3H-compounds showed that angiotensin II caused a proportionate increase in stimulation-evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine; this finding rules out any inhibition of noradrenaline uptake mechanisms. 6. 10−4–10−3 M acetylcholine caused hexamethonium-sensitive acceleration of basal tritium outflow. Much lower concentrations (10−7 M and higher) reduced the overflow evoked by electrical stimulation. The evoked overflow of 3H-noradrenaline, 3H-DOPEG, and 3H-normetanephrine was proportionately decreased. The depression was antagonized by atropine. Very low concentrations of acetylcholine (10−11–10−10 M) produced no change irrespective of whether the superfusion fluid contained cocaine and corticosterone or not. 7. Prostaglandins E1, E2, B2, and F2α reduced the evoked overflow of tritium. PGB2 and PGF2α were about 300 times less potent than the prostaglandins E. Indometacin caused a slight increase. 8. Morphine, histamine, serotonin, and substance P did not change the stimulation-evoked overflow (in the presence of cocaine and corticosterone). 9. It is concluded that the noradrenergic neurones of the rabbit pulmonary artery are endowed with presynaptic α-adrenoceptors as well as angiotensin, nicotine, muscarine, and prostaglandin receptors. No evidence was obtained for presynaptic β-adrenoceptors, dopamine, and morphine receptors, nor for a presynaptic facilitatory effect of prostaglandins or picomolar concentrations of acetylcholine. This pattern differs from that found in other organs, thus substantiating marked tissue differences in presynaptic receptor systems.

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