Cl- secretion induced by 5-hydroxytryptamine and calcitonin gene-related peptide in rat tracheal epithelia.
The effects of 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), which are colocalized in nerve terminals in the airway, on Cl- secretion in rat tracheal epithelia were tested. Short-circuit current (Isc) was measured after rat tracheal epithelial monolayers were cultured on porous filters. In rat tracheal monolayers 5-HT and CGRP increased Isc upon addition to the serosal compartment, in a dose-dependent manner with EC50 values at 5 micromol/l and 5 nmol/l, respectively. The responses were dependent on the presence of Cl- in the bathing solution and were inhibited by 100 micromol/l bumetanide. When 5-HT or CGRP was added after the administration of forskolin, the responses were not observed. 5-HT and CGRP increased the intracellular cAMP concentration. Low-Ca2+ buffer (0.1 mmol/l) and pretreatment with BAPTA/AM (10 micromol/l), thapsigargin (1 micromol/l) or indomethacin (10 micromol/l) did not affect the responses to 5-HT and CGRP. The 5-HT-induced response was not inhibited by 5-HT2 and/or 5-HT4 antagonists. These results indicate that in the rat tracheal epithelia 5-HT and CGRP increase Cl- secretion by an increase in intracellular cAMP concentration via direct activation of basolateral receptors, and that the response to 5-HT is not mediated via 5-HT4 receptors.
Jung
J S
JS
Department of Physiology, College of Medicine, Pusan National University, 1 Ga, Ami-Dong, Suh-Gu, Pusan, Korea.
Oh
S O
SO
Kim
M G
MG
Kang
D S
DS
Lee
S H
SH
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism*
D002712:Chlorides; D002034:Bumetanide; D005576:Colforsin; D012701:Serotonin; D004533:Egtazic Acid; D019284:Thapsigargin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007213:Indomethacin