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

Abstract

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...

Prejunctional β‐adrenoceptors in rabbit pulmonary artery and mouse atria: effect of α‐adrenoceptor blockade and phosphodiesterase inhibition

“…At very low or near maximal endogenous synthesis rates of cyclic AMP, phosphodiesterase inhibition may have little effect. Starke et al (1975) and Endo et al (1977) extensively studied 0-adrenoceptor enhancement of noradrenaline release in the rabbit pulmonary artery at various frequencies of electrical stimulation and concluded that prejunctional P-adrenoceptors were not functional in this tissue. In the present study, in rabbit pulmonary artery incubated with [3H]-noradrenaline and stimulated at 1 Hz, isoprenaline alone also failed to enhance the S-I outflow of radioactivity.…”

The Effects of Piperoxan on Uptake of Noradrenaline and Overflow of Transmitter in the Isolated Blood Perfused Spleen of the Cat

“…increase in overflow must be due to an increase in transmitter liberation by the nerves. The simplest explanation for this is an inhibition of the presynaptic inhibitory a-adrenoceptors on the noradrenergic nerves (see Endo, Starke, Bangerter & Taube, 1977). The net effect upon the response of the inhibition of pre-and postsynaptic a-adrenoceptors will be determined by the relative potency of the antagonist at the two receptor sites.…”

Vascular injury augments adrenergic neurotransmission.

“…A 2F Fogarty arterial embolectomy catheter (Baxter Health Care Co, Santa Ana, Calif) was inserted into the artery and advanced proximally into the iliac artery past the bifurcation into the aorta. The 16 OOOg in a microfuge for 5 minutes.…”