Serotonin via 5-HT1B and 5-HT2B receptors stimulates anion secretion in the rat epididymal epithelium.
1. The 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. 2. 5-HT, the 5-HT1B-selective agonist 5-nonyloxytryptamine (5-NOT) and the 5-HT2B-selective agonist alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) added basolaterally stimulated Isc in a dose-dependent manner with EC50 values of 0.4, 20 and 0.3 microM, 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-HT1B-selective antagonist isamoltane (200 microM) and the 5-HT2B-selective antagonist rauwolscine (200 microM) 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 alpha-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. 5. Manipulation of the cAMP and Ca2+ signal transduction pathways with chemical agents provided evidence that the responses to 5-HT were mediated through cAMP. 6. Piroxicam pretreatment abolished the Isc response to alpha-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. 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.
Leung
G P
GP
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Dun
S L
SL
Dun
N J
NJ
Wong
P Y
PY
D000818:Animals; D000838:Anions / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004822:Epididymis / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D007097:Imines / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013449:Sulfonamides; D019284:Thapsigargin / Q000494:pharmacology
D000838:Anions; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007097:Imines; D007546:Isoquinolines; D044302:Receptor, Serotonin, 5-HT1B; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D013449:Sulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D005576:Colforsin; D012701:Serotonin; D004533:Egtazic Acid; D019284:Thapsigargin; C014925:RMI 12330A; D000242:Cyclic AMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide