Functional evidence that [3H]acetylcholine and [3H]noradrenaline release from guinea pig ileal myenteric plexus and noradrenergic terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes

C. Blandizzi, G. Tarkovacs, G. Natale, M. Del Tacca, E. Vízi

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Abstract

The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and α-methyl-noradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 μM, 0.88 μM, 0.93 μM and 0.83 μM, respectively. Idazoxan (1 μM), CH 38083 (1 μM), WB 4101 (1 μM), prazosin (1-10 μM) and ARC 239 (1-10 μM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated K(B) values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 μM), xylazine (0.1-100 μM), detomidine (0.1-100 μM) or α-methyl-noradrenaline (0.1-100 μM), whereas it was enhanced by idazoxan (0.1-100 μM), CH 38083 (0.1-100 μM), WB 4101 (0.1-100 μM), prazosin (0.1 μM) and ARC 239 (0.1-100 μM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine ≥ detomidine > α-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 ≥ idazoxan > CH 38083 > WB 4101 for antagonists. The present results provide functional evidence that [3H]acetylcholine and [3H]noradrenaline release from axon terminals of guinea pig ileum myenteric plexus and noradrenergic axon terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes. On the basis of the criteria currently adopted for the classification of alpha-2 adrenoceptor subtypes, it is suggested that hetero- and auto-alpha-2 adrenoceptors investigated in the present study may resemble the alpha-2A- and alpha-2B-binding sites, respectively.

Original languageEnglish
Pages (from-to)1054-1060
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number3
Publication statusPublished - 1993

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Myenteric Plexus
Adrenergic Receptors
Acetylcholine
Norepinephrine
Guinea Pigs
Idazoxan
Oxymetazoline
Xylazine
Prazosin
Ileum
Tritium
Presynaptic Terminals
Choline
Inhibitory Concentration 50
Binding Sites
Muscles
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
7,8-(methylenedioxy)-14-hydroxyberbane
AR-C239
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{82a980cecd8b485595ec1cb875bf30bc,
title = "Functional evidence that [3H]acetylcholine and [3H]noradrenaline release from guinea pig ileal myenteric plexus and noradrenergic terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes",
abstract = "The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and α-methyl-noradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 μM, 0.88 μM, 0.93 μM and 0.83 μM, respectively. Idazoxan (1 μM), CH 38083 (1 μM), WB 4101 (1 μM), prazosin (1-10 μM) and ARC 239 (1-10 μM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated K(B) values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 μM), xylazine (0.1-100 μM), detomidine (0.1-100 μM) or α-methyl-noradrenaline (0.1-100 μM), whereas it was enhanced by idazoxan (0.1-100 μM), CH 38083 (0.1-100 μM), WB 4101 (0.1-100 μM), prazosin (0.1 μM) and ARC 239 (0.1-100 μM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine ≥ detomidine > α-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 ≥ idazoxan > CH 38083 > WB 4101 for antagonists. The present results provide functional evidence that [3H]acetylcholine and [3H]noradrenaline release from axon terminals of guinea pig ileum myenteric plexus and noradrenergic axon terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes. On the basis of the criteria currently adopted for the classification of alpha-2 adrenoceptor subtypes, it is suggested that hetero- and auto-alpha-2 adrenoceptors investigated in the present study may resemble the alpha-2A- and alpha-2B-binding sites, respectively.",
author = "C. Blandizzi and G. Tarkovacs and G. Natale and {Del Tacca}, M. and E. V{\'i}zi",
year = "1993",
language = "English",
volume = "267",
pages = "1054--1060",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Functional evidence that [3H]acetylcholine and [3H]noradrenaline release from guinea pig ileal myenteric plexus and noradrenergic terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes

AU - Blandizzi, C.

AU - Tarkovacs, G.

AU - Natale, G.

AU - Del Tacca, M.

AU - Vízi, E.

PY - 1993

Y1 - 1993

N2 - The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and α-methyl-noradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 μM, 0.88 μM, 0.93 μM and 0.83 μM, respectively. Idazoxan (1 μM), CH 38083 (1 μM), WB 4101 (1 μM), prazosin (1-10 μM) and ARC 239 (1-10 μM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated K(B) values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 μM), xylazine (0.1-100 μM), detomidine (0.1-100 μM) or α-methyl-noradrenaline (0.1-100 μM), whereas it was enhanced by idazoxan (0.1-100 μM), CH 38083 (0.1-100 μM), WB 4101 (0.1-100 μM), prazosin (0.1 μM) and ARC 239 (0.1-100 μM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine ≥ detomidine > α-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 ≥ idazoxan > CH 38083 > WB 4101 for antagonists. The present results provide functional evidence that [3H]acetylcholine and [3H]noradrenaline release from axon terminals of guinea pig ileum myenteric plexus and noradrenergic axon terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes. On the basis of the criteria currently adopted for the classification of alpha-2 adrenoceptor subtypes, it is suggested that hetero- and auto-alpha-2 adrenoceptors investigated in the present study may resemble the alpha-2A- and alpha-2B-binding sites, respectively.

AB - The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and α-methyl-noradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 μM, 0.88 μM, 0.93 μM and 0.83 μM, respectively. Idazoxan (1 μM), CH 38083 (1 μM), WB 4101 (1 μM), prazosin (1-10 μM) and ARC 239 (1-10 μM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated K(B) values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 μM), xylazine (0.1-100 μM), detomidine (0.1-100 μM) or α-methyl-noradrenaline (0.1-100 μM), whereas it was enhanced by idazoxan (0.1-100 μM), CH 38083 (0.1-100 μM), WB 4101 (0.1-100 μM), prazosin (0.1 μM) and ARC 239 (0.1-100 μM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine ≥ detomidine > α-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 ≥ idazoxan > CH 38083 > WB 4101 for antagonists. The present results provide functional evidence that [3H]acetylcholine and [3H]noradrenaline release from axon terminals of guinea pig ileum myenteric plexus and noradrenergic axon terminals is modulated by different presynaptic alpha-2 adrenoceptor subtypes. On the basis of the criteria currently adopted for the classification of alpha-2 adrenoceptor subtypes, it is suggested that hetero- and auto-alpha-2 adrenoceptors investigated in the present study may resemble the alpha-2A- and alpha-2B-binding sites, respectively.

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