Mechanisms underlying presynaptic inhibition through alpha 2‐adrenoceptors in guinea‐pig submucosal neurones.

Abstract

Idazoxan and yohimbine competitively antagonized the action of noradrenaline with dissociation equilibrium constants of 20 and 30 nm respectively.3. In another series of experiments, noradrenaline and somatostatin were applied locally from a pipette so that they reached presynaptic terminals but not the cell bodies or axons of the presynaptic cell: noradrenaline inhibited EPSPs by 90 % in all neurones but somatostatin had no effect. When applied locally to the cell bodies giving rise to the presynaptic fibres, both agonists inhibited EPSPs in half the neurones by 40 %.4. When noradrenaline was applied locally to presynaptic terminals, the latency to onset of noradrenaline to inhibit EPSPs was 45-160 ms; cadmium applied similarly depressed EPSPs in 5-50 ms. 5. Pertussis toxin pre-treatment only partially blocked presynaptic inhibition caused by noradrenaline but abolished the reduction of EPSP amplitude by somatostatin.6. It is concluded that noradrenaline and somatostatin reduce the amplitude of the fast EPSP because they hyperpolarize cell bodies and prevent action potential initiation. Noradrenaline, but not somatostatin, has an additional action to inhibit acetylcholine release by acting at nerve terminal receptors.7. The presynaptic inhibitory action of noradrenaline results from activation of a2-adrenoceptors at nerve terminals but the mechanism(s) by which these presynaptic receptors act cannot be explained adequately by either activation of a potassium conductance and/or inhibition of a calcium conductance.MS 8372 20PHY 431

Differential localization of Ca2+ channel ?1 subunits in the enteric nervous system: Presence of ?1B channel-like immunoreactivity in intrinsic primary afferent neurons

“…Several studies have shown that -CTx GVIA reduces the release of both ACh and several neuropeptides from guinea pig enteric nerves, and diminishes fast nicotinic excitatory postsynaptic potentials (EPSPs; Lundy and Frew, 1988;Shen and Surprenant, 1990). Our findings are consistent with these studies, which suggest that -CTx GVIA-sensitive channels are present in nerve terminals in the guinea pig ileum.…”

Presynaptic modulation of cholinergic and non‐cholinergic fast synaptic transmission in the myenteric plexus of guinea pig ileum

“…Previous studies have shown that 5‐HT 1A receptors also mediate inhibition of fEPSPs in the myenteric plexus but these studies did not identify the pharmacological properties of the synaptic responses 13,14 . Similarly, it has been established that α2‐adrenergic receptors mediate presynaptic inhibition of cholinergic and non‐cholinergic synaptic transmission in the intestine and that α2 adrenergic receptor agonists inhibit fEPSPs in the enteric nervous system 11,22,23 . However, the pharmacological properties of fEPSPs inhibited by α2 adrenergic receptor agonists were not identified.…”

The μ‐opioid receptor: an electrophysiologist's perspective from the sharp end

“…There has been much debate about the relative importance of potassium channel activation and inhibition of voltage‐activated calcium channels in presynaptic G i/o ‐coupled receptor‐mediated inhibition of neurotransmitter release (see e.g. Shen and Surprenant, ; Vaughan and Christie, ; Vaughan et al ., ). It would appear that μ‐opioid receptor activation can also directly inhibit the neurotransmitter release machinery independent of any effect on membrane conductances (Capogna et al ., ) given that μ‐opioid receptor activation reduced the miniature GABAergic inhibitory synaptic currents evoked by the calcium ionophore ionomycin, that is, by direct calcium entry into the nerve terminals (Capogna et al ., ; Bergevin et al ., ).…”