title: Long-term facilitation of peptidergic transmission by catecholamines in guinea-pig inferior mesenteric ganglia.
abstract: 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.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D010455:Peptides; D013373:Substance P; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine