Functional characterization of neuronal pre and postsynaptic alpha 2-adrenoceptor subtypes in guinea-pig submucosal...

1. The alpha 2-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 2 s) 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 microM) altered any of the three responses to alpha 2-adrenoceptor agonists. 6. It is concluded that alpha 2-adrenoceptors present on submucosal neuronal cell bodies, on presynaptic cholinergic nerve terminals and on presynaptic sympathetic nerve terminals are the alpha 2A subtype. However, functional characterization of this subtype differs from that provided by ligand binding studies.