Muscarine receptors on the rat phrenic nerve, evidence for positive and negative muscarinic feedback mechanisms

Abstract

Neuronal transmitter stores of the rat phrenic nerve were labelled by incubation with [3H]choline. Release of [3H]acetylcholine was elicited by electrical nerve stimulation (100 or 1,500 pulses, 5 or 25 Hz) or by high potassium (27 mmol/l) and the effects of the muscarine receptor agonist oxotremorine and the antagonist scopolamine were investigated. Neither oxotremorine nor scopolamine affected the basal tritium efflux. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration of oxotremorine (1 mumol/l) reduced the electrically evoked [3H]acetylcholine release. Likewise, the high potassium-evoked [3H]acetylcholine release was reduced by a high concentration of oxotremorine. Both effects of oxotremorine, increase and decrease, were abolished by a pretreatment (30 min before the first stimulation period) with 0.1 mumol/l scopolamine. Scopolamine (0.1 mumol/l) alone, enhanced [3H]acetylcholine release evoked by 100 pulses (5 Hz) or by high potassium. Scopolamine, however, reduced [3H]acetylcholine release evoked by 1,500 pulses (5 Hz or 25 Hz). The concentration-response curves obtained for scopolamine under these latter stimulation conditions were flat-running and biphasic which might indicate the involvement of two opposite effects (increase and decrease) of scopolamine under the present stimulation conditions. Both effects of scopolamine were reduced in the presence of 10 mumol/l neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenthonium, a quaternary derivative of (−)−hyoscyamine, enhances the spontaneous release of acetylcholine at rat motor nerve terminals

“…The type of cholinoceptor sites involved in the feedback regulation however, is controversial. Muscarinic inhibitory (Duncan & Publicover, 1979;Michaelson et al, 1979;Abbs & Joseph, 1981;Somogyi et al, 1987) and excitatory (Das et al, 1978;Wali et al, 1987;Wessler et al, 1987) prejunctional cholinoceptors have been reported at vertebrate neuromuscular junctions and in the Torpedo electric organ. In the presence of tubocurarine, a frequency-dependent decrease of evoked ACh release was obtained which suggested the presence of nicotinic prejunctional cholinoceptors mediating a positive feedback control of evoked transmitter release (Glavinovic, 1979a;Magleby et al, 1981;Wessler et al, 1986;Matzner et al, 1988).…”

Mapping of five subtype genes for muscarinic acetylcholine receptor to mouse chromosomes.

“…This process starts at the endplates and advances proximally. Because it was reported that the presynaptic membrane of the motor endplate has muscarinic autoreceptors which modulate the release of acetylcholine (Wessler et al, 1987), it is conceivable that deficit of these autoreceptors causes axonal degeneration in the pmn homozygote. It is worth noting that treatment with ciliary neurotrophic factor (CNTF) prevented the degeneration of motor neuron in the pmn homozygote (Sendtner et al, 1992).…”

Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: link between positive (nicotinic)− and negative (muscarinic)‐feedback modulation

“…In addition, electrophysiological (Beranek & Vyskocil, 1967) and histochemical data (Gillberg et al, 1984) oppose the presence of muscarinic receptors at the neuromuscular junction. Wessler et al (1987b) found that the stimulation by oxotremorine of muscarinic receptors resulted in a biphasic response: in low concentrations (10 nM) oxotremorine enhanced whereas in higher concentrations (1 pM) it inhibited the release of ACh. These data and our earlier observations that oxotremorine reduces the release of ACh (Vizi et al, 1985; suggest that the release of ACh from the neuromuscular junction is modulated by muscarinic receptors.…”

“…However, it has been shown that the muscarinic receptor agonist oxotremorine reduced , and the antagonist atropine enhanced Wessler et al, 1987b) the release of ACh evoked by electrical stimulation. This suggests that negative feedback modulation mediated via muscarinic receptors occurs at the neuromuscular junction Wessler et al, 1987b).…”

“…This suggests that negative feedback modulation mediated via muscarinic receptors occurs at the neuromuscular junction Wessler et al, 1987b). In this study an attempt was made to investigate the possible interaction between muscarinic autoinhibition and nicotinic receptor-mediated positive feedback modulation of ACh release at prejunctional axon terminals of the mouse hemidiaphragm preparation.…”