Inhibitory synaptic potentials resulting from alpha 2‐adrenoceptor activation in guinea‐pig submucous plexus neurones.

Abstract

SUMMARY1. Intracellular recordings were obtained from neurones of the guinea-pig submucous plexus. Inhibitory synaptic potentials (i.p.s.p.s) were compared with hyperpolarizations evoked by brief, local applications of noradrenaline and by superfusion with adrenoceptor agonists.2. Hyperpolarizing potentials elicited by brief applications of noradrenaline were similar to the i.p.s.p. in latency of onset, amplitude, time course, conductance increase, reversal potential and ionic dependence. Both responses were blocked by low concentrations of Ba2+ and quinine.3. 6-hydroxydopamine selectively and irreversibly abolished the i.p.s.p. and resulted in a complete loss of catecholamine fluorescent nerve fibres in the submucous plexus.4. The a2-adrenoceptor antagonists, phentolamine, yohimbine and RX781094, reversibly blocked the i.p.s.p. and the noradrenaline hyperpolarization. Prazosin, propranolol, atropine and naloxone had no effect on these responses.5. Superfusion with noradrenaline and clonidine produced dose-dependent membrane hyperpolarizations. Noradrenaline and clonidine dose-hyperpolarization curves were shifted to the right in a parallel fashion by a2-adrenoceptor antagonists.6. Determination of the dissociation equilibrium constants for phentolamine, yohimbine and RX781094 showed that the hyperpolarization produced by noradrenaline perfusion is due to a2-adrenoceptor activation.7. It is concluded that the release of noradrenaline from sympathetic nerves activates post-synaptic LZ2-adrenoceptors, resulting in the K+ conductance increase which underlies the i.p.s.p. in submucous plexus neurones.

Vasoconstriction of guinea‐pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP

“…Previous studies have characterized the i.p.s.p. recorded in normal preparations as being due to the action of NA released from sympathetic nerves onto a2-adrenoceptors on the submucosal neurones (North & Surprenant, 1985), although a non-adrenergic i.p.s.p. has also been observed (Mihara et al, 1987;Bornstein et al, 1988).…”

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

“…Methods of dissection, intracellular recording from submucosal neurones, stimulation of interganglionic nerve fibres and optical measurements of arteriolar diameter have been described in detail previously (Surprenant, 1984;Neild et al, 1990 Ltd, 1990 nist; previous studies have shown that cumulative and noncumulative applications of UK 14304 produce similar hyperpolarizations in submucosal neurones (North & Surprenant, 1985;Surprenant & North, 1988). Schild plots were obtained from data on individual neurones and the dissociation equilibrium constants (KDs) and slopes so obtained were then averaged.…”

“…Previous determinations of KD values for idazoxan, yohimbine and phentolamine for the receptors involved in postsynaptic hyperpolarization indicated that a homogeneous population of o2-adrenoceptors was present on submucosal neurones (North & Surprenant, 1985;Surprenant & North, 1988). Slopes of Schild plots for idazoxan, yohimbine, WB 4101 and ARC-239 to antagonize the UK 14304 inhibition of the nicotinic e.p.s.p.…”

“…ceptor mediating membrane hyperpolarization in submucosal neurones has been shown to be an a2-adrenoceptor (North & Surprenant, 1985;Surprenant & North, 1988); presynaptic adrenoceptors mediating both inhibition of acetylcholine release onto submucosal neurones and inhibition of sympathetically released transmitter onto submucosal arterioles are also likely to be a2-adrenoceptors (Surprenant, 1989). We were interested in determining whether postsynaptic neuronal a2-adrenoceptors were identical to presynaptic a2-adrenoceptors and whether these adrenoceptors could be classified with ligands which have been shown to be selective in binding studies.…”

“…Noradrenaline hyperpolarizes submucosal neurones, inhibits the release of acetylcholine from (cholinergic) submucosal neurones as well as the release of sympathetically released neurotransmitter onto submucosal arterioles (North & Surprenant, 1985;Suprenant, 1989;Hirst, 1989). The postsynaptic adreno-I Author for correspondence.…”