Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery.
A search was performed for presynaptic, release-modulating receptor systems on the post-ganglionic 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 overflow of tritium, thus confirming selective release from noradrenergic neurones. 49% of the stimulation-evoked overflow of total consisted of 3H-noradrenaline, 22% of 3H-3,4-dihydroxyphenyglycol (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 stimulation-evoked overflow of total tritium. The overflow evoked per pulse was 2.2 X 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 alpha-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 alpha-adrenergic inhibiton. 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 alpha-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 alpha-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...
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D011817:Rabbits; D011955:Receptors, Drug / Q000187:drug effects
D002395:Catecholamines; D011453:Prostaglandins; D011955:Receptors, Drug; D000804:Angiotensin II; D001285:Atropine; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin