Microelectrode recording of the effects of agonists and antagonists on α‐adrenoceptors on rat somatic nerve terminals

Abstract

The effects of apomorphine, catechol, clonidine, isoprenaline, (‐)‐and (±)‐noradrenaline, phenylephrine, pyrogallol and xylazine were investigated on the frequency and amplitude of miniature endplate potentials (m.e.p.ps) and, with the exception of apomorphine, catechol and pyrogallol, on the amplitude of endplate potentials (e.p.ps) in the rat phrenic nerve diaphragm preparation. Clonidine, (‐)‐noradrenaline, phenylephrine and xylazine (each at 1.5 × 10−5M) increased m.e.p.p. frequency but not amplitude. The other drugs were ineffective, except isoprenaline (1.5 × 10−5 M) which enhanced m.e.p.p. amplitude but not frequency. The increase in m.e.p.p. frequency was inhibited by phentolamine, prazosin and yohimbine (each 1.5 × 10−9M). Prazosin and yohimbine alone each reduced m.e.p.p. frequency but failed to abolish m.e.p.ps even at high concentrations (10−3M). Clonidine, (‐)‐noradrenaline, phenylephrine and xylazine (each 3 × 10−6M) enhanced e.p.p. amplitude; this enhancement was blocked by prazosin and by yohimbine (each 3 × 10−6M). In preparations fatigued by prolonged continuous nerve stimulation (5 Hz, 0.05 ms for 30 min), (‐)‐noradrenaline (3.3 × 10−4M) restored m.e.p.p. frequency. The results indicate that adrenoceptors on somatic nerve terminals interact with both α1‐ and α2‐agonists and antagonists and show different characteristics from those at autonomic neuroeffector junctions. The α‐adrenoceptors on somatic nerve terminals may have an ancilliary physiological role in influencing but not controlling transmitter release.

Octopamine enhances neuromuscular transmission in developing and adult moths, Manduca sexta

“…Both noradrenaline and adrenaline increase the amplitude of the end-plate potential of rat diaphragm muscle; the greater effect occurs with noradrenaline (Kuba, 1970;Kuba and Tomita, 1971). Similar results are obtained with ( -)-noradrenaline and various adrenoceptor agonists (Malta, McPherson, and Raper, 1979;Lim and Muir, 1983). The amplitude of the EJP in frog muscle is likewise increased by noradrenaline (Jenkinson, Stamenovic, and Whitaker, 1968).…”

Transduction of the modulatory effect of catecholamines at the mammalian motor neuron terminal

“…Authors using relatively high [Ca2+Io (2.5-2.7 mM) were able to obtain a statistically significant increase in MEPP(f) (Kuba, 1970. Lim andMuir, 1983). Others, using up to 2 mM [Ca2'] either did not apply statistics or, in the case of Miyamoto and Breckenridge (19741, found that the increase in MEPP(f) was not statistically significant.…”

“…Yohimbine blocked not only this effect but also the response to phenylephrine (PE) (Lim and Muir, 1983).…”

Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction

“…α2-adrenoceptor activation by clonidine and xylazine also caused an increase in MEPP frequency at the rat diaphragm NMJ, and it was eliminated by α-adrenoceptor blockers phentolamine, prazosin and yohimbine, suggesting the presence of presynaptic α1- and α2-adrenoceptors [ 28 ]. Two sympathomimetic agents used in clinical practice, salbutamol and clenbuterol, activated β2-adrenoceptors and induced the elevation of spontaneous ACh secretion in mouse preparations of peroneal nerves and lumbricalis muscles [ 9 , 29 ].…”

“…Snider and Gerald [ 41 ], using a radioenzymatic assay, showed an increase in nerve-stimulated ACh release induced by noradrenaline via presynaptic α1-adrenoceptors. However, noradrenaline did not cause any change in the evoked quantal secretion in the experiments of Lim and Muir [ 28 ], whereas clonidine, phenylephrine and xylazine enhanced EPP amplitude, which was blocked by prazosin and yohimbine. In Chiou and Chang’s [ 42 ] experiments, the EPP quantal content was unaffected by clonidine, although the amplitudes of EPPs and MEPPs were markedly decreased.…”