Long‐term facilitation of peptidergic transmission by catecholamines in guinea‐pig inferior mesenteric ganglia.

Intracellular recordings were obtained from neurones of isolated guinea‐pig inferior mesenteric ganglia. Repetitive stimulation (10‐20 Hz for 1‐2 s) of the hypogastric nerves evoked, in addition to the fast excitatory post‐synaptic potential (e.p.s.p.), a non‐cholinergic e.p.s.p. the mediator of which has previously been suggested to be substance P or a related peptide. When applied to the ganglia in the concentrations of 1‐100 microM for 3‐5 min, adrenaline, isoprenaline and noradrenaline produced an initial, short‐lasting depression which was followed by a marked augmentation of the non‐cholinergic e.p.s.p. lasting from minutes to over hours. Employed in comparable concentrations dopamine caused a slight depression that was not followed by a detectable increase of the non‐cholinergic e.p.s.p. The catecholamine‐induced depression and subsequent enhancement of the non‐cholinergic e.p.s.p. was prevented by alpha‐adrenergic antagonists (dihydroergotamine and phenoxybenzamine, 1‐10 microM) and beta‐adrenergic antagonists (propranolol and dichlorisoprenaline, 5‐10 microM), respectively. The membrane depolarization induced by the putative transmitter substance P (1 microM) was augmented by isoprenaline; the enhancement which could be blocked by beta‐antagonists was not preceded by a depression. Application of dibutyryl cyclic AMP (10 microM‐1 mM) by either superfusion or intracellular ionophoresis mimicked the enhancing effect of catecholamines. It is concluded that catecholamines, with the noticeable exception of dopamine, exerted a biphasic effect on the non‐cholinergic e.p.s.p. of the inferior mesenteric ganglion cells: an initial depression that was mediated by alpha‐adrenergic receptors and probably reflected a presynaptic inhibitory effect of catecholamines and, on the other hand, an enduring facilitation mediated by beta‐adrenergic receptors which appeared to be linked to activation of post‐ganglionic cyclic AMP.