Functional characterization of neuronal pre and postsynaptic α2-adrenoceptor subtypes in guinea-pig submucosal plexus

Ke-Zhong Shen, C. Barajas-Lopez, A. Surprenant

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

1. The α2-adrenoceptors on cell bodies of submucosal neurones, on presynaptic cholinergic nerve terminals innervating submucosal neurones, and on presynaptic sympathetic fibres innervating submucosal arterioles were characterized in functional studies by use of subtype selective ligands. 2. Both membrane hyperpolarization and presynaptic inhibition of nicotinic excitatory synaptic potentials (e.p.s.ps) produced by UK 14304 were similarly antagonized by idazoxan, yohimbine, SKF 104078, WB 4101 and ARC-239. Antagonism was competitive and dissociation equilibrium constants were the same for both effects. 3. Vasoconstriction of submucosal arterioles in response to stimulation of the sympathetic nerves (20 Hz for 2s) was inhibited by UK 14304 and clonidine; concentrations producing half-maximum responses were 6 nM and 10 nM respectively. Idazoxan, yohimbine, WB 4101 and SKF 104078 antagonized this action, with dissociation constants similar to those for antagonism of the postsynaptic membrane hyperpolarization and presynaptic inhibition of nicotinic e.p.s.ps. 4. Oxymetazoline was a partial agonist when membrane hyperpolarization or presynaptic inhibition of nicotinic e.p.s.ps were measured but a full agonist when presynaptic inhibition of sympathetically-mediated arteriolar vasoconstriction was measured. As an agonist, oxymetazoline produced half maximum responses at 80-120 nM; the dissociation constant for oxymetazoline as an antagonist was 130 nM. 5. Neither prazosin nor chlorpromazine (up to 30 μM) altered any of the three responses to α2-adrenoceptor agonists. 6. It is concluded that α2-adrenoceptors present on submucosal neuronal cell bodies, on presynaptic cholinergic nerve terminals and on presynaptic sympathetic nerve terminals are the α(2A) subtype. However, functional characterization of this subtype differs from that provided by ligand binding studies.

Original languageEnglish (US)
Pages (from-to)925-931
Number of pages7
JournalBritish Journal of Pharmacology
Volume101
Issue number4
StatePublished - 1990

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Oxymetazoline
Submucous Plexus
Adrenergic Receptors
Idazoxan
Guinea Pigs
Yohimbine
Arterioles
Vasoconstriction
Cholinergic Agents
Membranes
Ligands
Adrenergic Fibers
Neurons
Synaptic Potentials
Prazosin
Chlorpromazine
Presynaptic Terminals
Clonidine
Brimonidine Tartrate
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane

ASJC Scopus subject areas

  • Pharmacology

Cite this

Functional characterization of neuronal pre and postsynaptic α2-adrenoceptor subtypes in guinea-pig submucosal plexus. / Shen, Ke-Zhong; Barajas-Lopez, C.; Surprenant, A.

In: British Journal of Pharmacology, Vol. 101, No. 4, 1990, p. 925-931.

Research output: Contribution to journalArticle

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