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1The short‐circuit current (Isc) technique was used to study the role of 5‐hydroxytryptamine (5‐HT) in the regulation of anion secretion in cultured rat cauda epididymal epithelia.25‐HT, the 5‐HT1B‐selective agonist 5‐nonyloxytryptamine (5‐NOT) and the 5‐HT2B‐selective agonist α‐methyl‐5‐hydroxytryptamine (α‐methyl‐5‐HT) added basolaterally stimulated Iscin a dose‐dependent manner with EC50values of 0.4, 20 and 0.3 μm, respectively. No other agonists for 5‐HT receptors had any effect.3The pattern of responses to 5‐HT was biphasic. Pretreating the tissues with the 5‐HT1B‐selective antagonist isamoltane (200 μm) and the 5‐HT2B‐selective antagonist rauwolscine (200 μm) inhibited the rapid transient phase by 55 and 45 %, whereas the sustained phase could only be blocked by rauwolscine.4Removal of chloride or bicarbonate or both from the normal Krebs‐Henseleit solution reduced the responses to 5‐HT, 5‐NOT and α‐methyl‐5‐HT to varying degrees. The results suggest that 5‐HT1B‐ and 5‐HT2B‐mediated responses were mainly due to chloride and bicarbonate secretion, respectively.5Manipulation of the cAMP and Ca2+signal transduction pathways with chemical agents provided evidence that the responses to 5‐HT were mediated through cAMP.6Piroxicam pretreatment abolished the Iscresponse to α‐methyl‐5‐HT but not to 5‐NOT, indicating that the 5‐HT2B‐mediated response, but not the 5‐HT1B‐mediated response, is dependent on prostaglandin synthesis.7Immunohistochemical studies showed that 5‐HT‐like immunoreactivity was detected in nerve fibres and in small granular cells surrounding the epididymal tubules.8It is suggested that the 5‐HT released from serotonergic nerve endings and/or from mast cells regulates electrolyte and fluid secretion in the epididymis.

The effects of capsaicin (0.5‐100 microM) on neurones of the isolated inferior mesenteric ganglia (i.m.g.) of the guinea‐pig were investigated by means of intracellular recording techniques. When applied to neurones of the i.m.g. that exhibited a slow non‐cholinergic excitatory potential (Dun & Jiang, 1982), capsaicin caused in the large majority of these cells a long lasting depolarization accompanied by intense neuronal discharges. During and immediately following the depolarization, repetitive presynaptic stimulation consistently failed to elicit the non‐cholinergic depolarization; a partial recovery was observed in relatively few neurones. The fast (nicotinic) excitatory post‐synaptic potentials (e.p.s.p.s) were not suppressed by capsaicin in any of these cells. The membrane potential, input resistance and the amplitude of fast e.p.s.p.s in neurones of the i.m.g. that generated no detectable non‐cholinergic depolarizations were not affected by capsaicin. Post‐synaptic membrane sensitivity to exogenous application of substance P was not altered following capsaicin superfusion even though the latter effectively abolished the non‐cholinergic depolarization in the same neurones. Superfusing the i.m.g. with a Ca‐free Krebs solution markedly attenuated or abolished the depolarizing effect of capsaicin whereas tetrodotoxin (1 microM) was without effect. Capsaicin was without effect in a few neurones that generated a non‐cholinergic depolarization; the latter was not desensitized by bath application of substance P. Capsaicin caused no appreciable effects in neurones of the bullfrog sympathetic ganglia; thus, the fast and slow post‐synaptic potentials including the late slow e.p.s.p. the transmitter of which is the peptide luteinizing hormone‐releasing hormone (Jan & Jan, 1982) were not affected. The results suggest that the depolarizing effect of capsaicin in neurones of the guinea‐pig i.m.g. is due to a selective release of ganglionic substance P or a substance P‐like peptide in a Ca‐dependent manner, and that the non‐cholinergic potentials elicited in capsaicin‐insensitive neurones may be generated by a transmitter(s) other than substance P.

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.