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-circui t current (I-SC) was measured after rat tracheal epithelial monolayers were cultured on porous filters. In rat tracheal monolayers 5-HT and CGRP increased I-SC upon addition to the serosal compartment, in a dos e-dependent manner with EC50 values at 5 mu mol/l and 5 nmol/l, respec tively. The responses were dependent on the presence of Cl- in the bat hing solution and were inhibited by 100 mu mol/l bumetanide. When 5-HT or CGRP was added after the administration of forskolin, the response s were not observed. 5-HT and CGRP increased the intracellular cAMP co ncentration. Low-Ca2+ buffer (0.1 mmol/l) and pretreatment with BAPTA/ AM (10 mu mol/l), thapsigargin (1 mu mol/l) or indomethacin (10 mu mol /l) did not affect the responses to 5-HT and CGRP. The 5-HT-induced re sponse was not inhibited by 5-HT2 and/or 5-HT4 antagonists. These resu lts 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.