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

Vízi, E. S.; Somogyi, George T.

doi:10.1111/j.1476-5381.1989.tb11924.x

Cited by 79 publications

(28 citation statements)

References 31 publications

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“…It is only when motor neurons are stimulated electrically at sufficiently high frequencies that nicotinic agonists are able to modulate acetylcholine release (Bowman et al. , 1988; Vizi & Somogyi, 1989; Wessler, 1989).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine

Dussor¹,

Leong

Gracia

et al. 2003

Eur J of Neuroscience

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Inflammation of the buccal mucosa, gingiva and periodontal tissues is a significant problem in users of nicotine-containing tobacco products; however, the potential role of nicotine in the development of this inflammation is unclear. In many tissues, nicotine, acting through nicotinic acetylcholine receptors (nAChRs), has been shown to increase the release of the pro-inflammatory mediator calcitonin gene-related peptide (CGRP) thereby potentially contributing to neurogenic inflammation. The purpose of the present studies was to determine the effects of nicotine and other nAChR agonists on capsaicin-evoked immunoreactive CGRP (iCGRP) release from rat buccal mucosa and to identify a potential cellular basis for these effects. Using a previously validated model of in vitro superfusion, we show that the nAChR agonists nicotine (EC50 557 micro m), epibatidine (EC50 317 pm) and cytisine (EC50 4.83 nm) potentiated capsaicin-evoked iCGRP release in a concentration-dependent manner by 123, 70 and 76%, respectively. The expression and distribution patterns of the mRNA transcripts encoding the alpha3, alpha4 and alpha6 nAChR subunits and their colocalization with CGRP and the capsaicin receptor VR1 were examined in rat trigeminal ganglion using combined in situ hybridization and immunohistofluorescence. Of all trigeminal neurons counted, mRNA encoding the alpha3, alpha4 and alpha6 subunits was found, respectively, in 14.45, 9.2 and 19.21% of neurons. The cell body diameter of most neurons containing any nAChR subunit was in the 30-40 micro m range with slightly fewer in the 20-30 micro m range. Co-localization of these alpha subunit transcripts with either CGRP or VR1 immunoreactivity ranged from approximately 5 to 7% for alpha4 and over 8% for alpha3 to 18% for alpha6. These data support the hypothesis that nicotinic agents, acting at nAChRs contained on primary sensory neurons, are capable of directly modulating the stimulated release of iCGRP. In the case of users of nicotine-containing tobacco products, this modulation could contribute to inflammatory processes within the oral cavity.

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Section: Discussionmentioning

confidence: 99%

Potentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine

Dussor¹,

Leong

Gracia

et al. 2003

Eur J of Neuroscience

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“…Consequently, blockade of this autoreceptor would inhibit the positive feedback control of ACh release resulting in a fade in muscle tension during rapid, repetitive nerve stimulation (Wessler et al, 1986;Gibb & Marshall, 1987;Bowman et al, 1988;Prior et al, 1995;Singh & Prior, 1998). Other studies have reported that d-TC, but not snake a-neurotoxins, produced a reduction in nerve-evoked 3 H-ACh release from rat nerve terminals during rapid and repetitive nerve stimulation, providing direct evidence that a presynaptic modulation of ACh release may be involved in the fade response produced by d-TC (Vizi & Somogyi, 1989;Wessler, 1992;Apel et al, 1995).…”

Section: Effects Of Candoxin On Twitch Responses Evoked By Tof Stimulmentioning

confidence: 89%

Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus)

Nirthanan

Charpantier

Gopalakrishnakone

et al. 2003

British J Pharmacology

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1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic a-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d-tubocurarine, and differs markedly from curaremimetic a-neurotoxins that produce little or no fade. 4 Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC 50 B10 nM) of oocyte-expressed muscle (abgd) nAChRs. Like a-conotoxin MI, well known for its preferential binding to the a/d interface of the muscle (abgd) nAChR, candoxin also demonstrated a biphasic concentration -response inhibition curve with a high-(IC 50 B2.2 nM) and a low-(IC 50 B98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (abgd) receptor. In contrast, curaremimetic a-neurotoxins have been reported to antagonize both binding sites with equal affinity.

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“…Although pre-junctional nicotinic receptors that facilitate acetylcholine release have been identified in the rat bladder, 6, 7 nicotinic receptors are not thought to directly mediate contraction of the normal bladder muscle.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular Nicotinic Receptors Mediate Bladder Contractions Following Bladder Reinnervation with Somatic to Autonomic Nerve Transfer after Decentralization by Spinal Root Transection

et al. 2015

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This study investigates whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway. Following bladder decentralization by transection of sacral roots, peripheral nerve transfer was performed with bilateral genitofemoral to pelvic nerve transfer (GFNT) and unilateral (left) femoral nerve to bilateral pelvic nerve transfer (FNT). Reinnervation was assessed 7.5 months post operatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots, and spinal cord. Of the 17 animals with GFNT, 14 (82%) demonstrated functional bladder reinnervation as evidenced by increased bladder pressure during stimulation of the transferred GFN or the L3 or L4 spinal ventral roots. Lumbar spinal cord stimulation caused increased bladder pressure in 9 of 10 (90%) animals with FNT. Succinylcholine (SCh) virtually eliminated bladder pressure increases induced by electrical stimulation of the transferred somatic nerves or the lumbar spinal segments that contribute axons to these donor nerves. In control animals (either un-operated or sham-operated) SCh had no effect on nerve evoked bladder pressure increases but substantially reduced urethra and anal sphincter pressure induced by stimulation of either the lumbosacral spinal cord or the S2-3 spinal ventral roots. The reinnervated detrusor muscles of GFNT and FNT animals also contained increased alpha1 nicotinic receptor subunit immunoreactivity in punctate dots on detrusor muscle fascicles and in neuronal cell bodies, staining not observed in control animals.

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

Cited by 79 publications

References 31 publications

Potentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine

Potentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine

Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus)

Neuromuscular Nicotinic Receptors Mediate Bladder Contractions Following Bladder Reinnervation with Somatic to Autonomic Nerve Transfer after Decentralization by Spinal Root Transection

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