Prejunctional nicotinic receptors involved in facilitation of stimulation-evoked noradrenaline release from the vas deferens of the guinea-pig

L. Todorov, K. Windisch, H. Shersen, A. Lajtha, M. Papasova, E. Vízi

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

1 In guinea-pig prostatic vas deferens loaded with [3H]-noradrenaline ([3H]-NA), nicotinic receptor agonists, nicotine and dimethylphenylpiperazinium (DMPP) enhanced the resting and facilitated the stimulation-evoked release of [3H]-NA in a concentration-dependent fashion. The effect of nicotine on both contraction of vas deferens and release of NA in response to field stimulation was stereospecific in favour of the naturally occurring (-)-enantiomer. Prolonged (15 min) exposure to (-)-nicotine resulted in acessation of the facilitatory effect on NA release and on responses of the vas deferens to field stimulation. 2 The rank order of agonist potency in facilitating NA release was DMPP = (-)-nicotine > (+)-nicotine. Cystisine had no agonistic activity. The dissociation constants (K(D)) of antagonists were 9.3 ± 0.6 and 31.4 ± 2.4 μM for (+)-tubocurarine and hexamethonium, respectively, when (-)-nicotine was used as agonist. α-Bungarotoxin had no antagonistic activity. These findings suggest that nicotinic receptors located on noradrenergic axon terminals are different from those located postsynaptically in striated muscle or ganglia but seem similar to those present on cholinergic axon terminals at the neuromuscular junction. 3 Cotinine, the breakdown product of nicotine failed to have any agonistic activity indicating that nicotine itself is responsible for the effects observed on axon terminals. 4 Stimulation of presynaptic muscarinic receptors by oxotremorine prevented the nicotine-induced facilitation of [3H]-NA release, indicating the presence of both inhibitory muscarinic and facilitatory nicotinic receptors on noradrenergic axon terminals.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalBritish Journal of Pharmacology
Volume102
Issue number1
Publication statusPublished - 1991

Fingerprint

Vas Deferens
Nicotinic Receptors
Nicotine
Norepinephrine
Guinea Pigs
Presynaptic Terminals
Dimethylphenylpiperazinium Iodide
Cholinergic Agents
Nicotinic Agonists
Oxotremorine
Presynaptic Receptors
Bungarotoxins
Cotinine
Tubocurarine
Hexamethonium
Striated Muscle
Neuromuscular Junction
Muscarinic Receptors
Ganglia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Prejunctional nicotinic receptors involved in facilitation of stimulation-evoked noradrenaline release from the vas deferens of the guinea-pig. / Todorov, L.; Windisch, K.; Shersen, H.; Lajtha, A.; Papasova, M.; Vízi, E.

In: British Journal of Pharmacology, Vol. 102, No. 1, 1991, p. 186-190.

Research output: Contribution to journalArticle

@article{70f08da9d0ec42fcbe815a22bbcdd7d8,
title = "Prejunctional nicotinic receptors involved in facilitation of stimulation-evoked noradrenaline release from the vas deferens of the guinea-pig",
abstract = "1 In guinea-pig prostatic vas deferens loaded with [3H]-noradrenaline ([3H]-NA), nicotinic receptor agonists, nicotine and dimethylphenylpiperazinium (DMPP) enhanced the resting and facilitated the stimulation-evoked release of [3H]-NA in a concentration-dependent fashion. The effect of nicotine on both contraction of vas deferens and release of NA in response to field stimulation was stereospecific in favour of the naturally occurring (-)-enantiomer. Prolonged (15 min) exposure to (-)-nicotine resulted in acessation of the facilitatory effect on NA release and on responses of the vas deferens to field stimulation. 2 The rank order of agonist potency in facilitating NA release was DMPP = (-)-nicotine > (+)-nicotine. Cystisine had no agonistic activity. The dissociation constants (K(D)) of antagonists were 9.3 ± 0.6 and 31.4 ± 2.4 μM for (+)-tubocurarine and hexamethonium, respectively, when (-)-nicotine was used as agonist. α-Bungarotoxin had no antagonistic activity. These findings suggest that nicotinic receptors located on noradrenergic axon terminals are different from those located postsynaptically in striated muscle or ganglia but seem similar to those present on cholinergic axon terminals at the neuromuscular junction. 3 Cotinine, the breakdown product of nicotine failed to have any agonistic activity indicating that nicotine itself is responsible for the effects observed on axon terminals. 4 Stimulation of presynaptic muscarinic receptors by oxotremorine prevented the nicotine-induced facilitation of [3H]-NA release, indicating the presence of both inhibitory muscarinic and facilitatory nicotinic receptors on noradrenergic axon terminals.",
author = "L. Todorov and K. Windisch and H. Shersen and A. Lajtha and M. Papasova and E. V{\'i}zi",
year = "1991",
language = "English",
volume = "102",
pages = "186--190",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Prejunctional nicotinic receptors involved in facilitation of stimulation-evoked noradrenaline release from the vas deferens of the guinea-pig

AU - Todorov, L.

AU - Windisch, K.

AU - Shersen, H.

AU - Lajtha, A.

AU - Papasova, M.

AU - Vízi, E.

PY - 1991

Y1 - 1991

N2 - 1 In guinea-pig prostatic vas deferens loaded with [3H]-noradrenaline ([3H]-NA), nicotinic receptor agonists, nicotine and dimethylphenylpiperazinium (DMPP) enhanced the resting and facilitated the stimulation-evoked release of [3H]-NA in a concentration-dependent fashion. The effect of nicotine on both contraction of vas deferens and release of NA in response to field stimulation was stereospecific in favour of the naturally occurring (-)-enantiomer. Prolonged (15 min) exposure to (-)-nicotine resulted in acessation of the facilitatory effect on NA release and on responses of the vas deferens to field stimulation. 2 The rank order of agonist potency in facilitating NA release was DMPP = (-)-nicotine > (+)-nicotine. Cystisine had no agonistic activity. The dissociation constants (K(D)) of antagonists were 9.3 ± 0.6 and 31.4 ± 2.4 μM for (+)-tubocurarine and hexamethonium, respectively, when (-)-nicotine was used as agonist. α-Bungarotoxin had no antagonistic activity. These findings suggest that nicotinic receptors located on noradrenergic axon terminals are different from those located postsynaptically in striated muscle or ganglia but seem similar to those present on cholinergic axon terminals at the neuromuscular junction. 3 Cotinine, the breakdown product of nicotine failed to have any agonistic activity indicating that nicotine itself is responsible for the effects observed on axon terminals. 4 Stimulation of presynaptic muscarinic receptors by oxotremorine prevented the nicotine-induced facilitation of [3H]-NA release, indicating the presence of both inhibitory muscarinic and facilitatory nicotinic receptors on noradrenergic axon terminals.

AB - 1 In guinea-pig prostatic vas deferens loaded with [3H]-noradrenaline ([3H]-NA), nicotinic receptor agonists, nicotine and dimethylphenylpiperazinium (DMPP) enhanced the resting and facilitated the stimulation-evoked release of [3H]-NA in a concentration-dependent fashion. The effect of nicotine on both contraction of vas deferens and release of NA in response to field stimulation was stereospecific in favour of the naturally occurring (-)-enantiomer. Prolonged (15 min) exposure to (-)-nicotine resulted in acessation of the facilitatory effect on NA release and on responses of the vas deferens to field stimulation. 2 The rank order of agonist potency in facilitating NA release was DMPP = (-)-nicotine > (+)-nicotine. Cystisine had no agonistic activity. The dissociation constants (K(D)) of antagonists were 9.3 ± 0.6 and 31.4 ± 2.4 μM for (+)-tubocurarine and hexamethonium, respectively, when (-)-nicotine was used as agonist. α-Bungarotoxin had no antagonistic activity. These findings suggest that nicotinic receptors located on noradrenergic axon terminals are different from those located postsynaptically in striated muscle or ganglia but seem similar to those present on cholinergic axon terminals at the neuromuscular junction. 3 Cotinine, the breakdown product of nicotine failed to have any agonistic activity indicating that nicotine itself is responsible for the effects observed on axon terminals. 4 Stimulation of presynaptic muscarinic receptors by oxotremorine prevented the nicotine-induced facilitation of [3H]-NA release, indicating the presence of both inhibitory muscarinic and facilitatory nicotinic receptors on noradrenergic axon terminals.

UR - http://www.scopus.com/inward/record.url?scp=0025853552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025853552&partnerID=8YFLogxK

M3 - Article

C2 - 2043921

AN - SCOPUS:0025853552

VL - 102

SP - 186

EP - 190

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -