Serotonin via 5‐HT 1B and 5‐HT 2B receptors stimulates anion secretion in the rat epididymal epithelium

1 The short‐circuit current ( I sc ) technique was used to study the role of 5‐hydroxytryptamine (5‐HT) in the regulation of anion secretion in cultured rat cauda epididymal epithelia. 2 5‐HT, the 5‐HT 1B ‐selective agonist 5‐nonyloxytryptamine (5‐NOT) and the 5‐HT 2B ‐selective agonist α‐methyl‐5‐hydroxytryptamine (α‐methyl‐5‐HT) added basolaterally stimulated I sc in a dose‐dependent manner with EC 50 values of 0.4, 20 and 0.3 μ m , respectively. No other agonists for 5‐HT receptors had any effect. 3 The pattern of responses to 5‐HT was biphasic. Pretreating the tissues with the 5‐HT 1B ‐selective antagonist isamoltane (200 μ m ) and the 5‐HT 2B ‐selective antagonist rauwolscine (200 μ m ) inhibited the rapid transient phase by 55 and 45 %, whereas the sustained phase could only be blocked by rauwolscine. 4 Removal 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‐HT 1B ‐ and 5‐HT 2B ‐mediated responses were mainly due to chloride and bicarbonate secretion, respectively. 5 Manipulation of the cAMP and Ca 2+ signal transduction pathways with chemical agents provided evidence that the responses to 5‐HT were mediated through cAMP. 6 Piroxicam pretreatment abolished the I sc response to α‐methyl‐5‐HT but not to 5‐NOT, indicating that the 5‐HT 2B ‐mediated response, but not the 5‐HT 1B ‐mediated response, is dependent on prostaglandin synthesis. 7 Immunohistochemical studies showed that 5‐HT‐like immunoreactivity was detected in nerve fibres and in small granular cells surrounding the epididymal tubules. 8 It is suggested that the 5‐HT released from serotonergic nerve endings and/or from mast cells regulates electrolyte and fluid secretion in the epididymis.