Serotonin activates electrolyte transport via 5-HT2A receptor in rat colonic crypt cells.
The aim of this study was to demonstrate that 5-HT activates electrolyte transport directly via 5-HT2A receptor in rat colonic crypt cells. Patch-clamp whole cell recording was performed in isolated crypts to measure the 5-HT-induced changes in electrogenic K+ and Cl- currents. Superfusing 5-HT (10 microM) in the bath solution increased both K+ and Cl- currents, which were antagonized by the presence of ketanserin (1 microM), a selective 5-HT2A antagonist, in the bath solution. Mesulergine (1 microM) a 5-HT2A and 5-HT2C antagonist, had no inhibitory effect. Strong chelation of the intracellular Ca2+ by 5 mM BAPTA inhibited 5-HT-induced currents. 5-HT also failed to activate K+ and C1- currents in the presence of GDPbetaS (0.5 mM) in the pipette solution. Intracellular administration of GTPgammaS (0.1 mM) mimicked the stimulatory effect of 5-HT, that was inhibited by 5 mM BAPTA. H-7 (0.05 mM), an inhibitor of protein kinase C, A, and G, did not affect the currents. These data indicate that a G protein-coupled pathway is involved in the activation of electrolyte secretion via 5-HT2A receptor.
Imada-Shirakata
Y
Y
First Department of Internal Medicine, Kyoto University, Japan.
Kotera
T
T
Ueda
S
S
Okuma
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004573:Electrolytes / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*
D002712:Chlorides; D004573:Electrolytes; D004873:Ergolines; D047428:Protein Kinase Inhibitors; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; C031649:mesulergine; D002118:Calcium