Serotonin-evoked calcium transients in airway smooth muscle cells.
Serotonin (5-HT) is an important mediator of allergic airway narrowing in several animal species. The present study was designed to characterize the receptor subtypes that mediate 5-HT-induced airway responses in the rat. To do this, we measured Ca2+ transients and adenosine 3',5'-cyclic monophosphate (cAMP) production evoked by 5-HT in cultured rat tracheal smooth muscle cells as well as 5-HT-induced contractions of isolated tracheal rings. 5-HT (10(-6) to 10(-4) M) triggered a rapid increase in intracellular Ca2+ concentration ([Ca2+]i) followed by a second phase of sustained, elevated, and sometimes oscillating levels of [Ca2+]i. Sustained but not peak [Ca2+]i levels were dependent on Ca2+ influx but were not attenuated by nifedipine (10(-5) M). Oscillations were observed in cells in Ca2+ -free medium, suggesting Ca2+ -induced Ca2+ release independent of Ca2+ influx. The effects of 5-HT were inhibited by thapsigargin (10(-6) M) and ketanserin (10(-7) M). In cells incubated with LY-278,584 (5-HT3 antagonist) and (-)pindolol (5-HT1 antagonist), 5-HT-evoked responses were not significantly different from the control values. 5-methyltryptamine (5-MT), a ligand with higher affinity for 5-HT2C receptors than "classical" 5-HT2 receptors, elicited higher responses than dipropyl-5-carboxamidotryptamine (DP-5-CT), which possesses lower affinity for 5-HT2C receptors than 5-MT, but an affinity for the classical 5-HT2 receptor similar to 5-MT, but an affinity for the classical 5-HT2 receptor similar to 5-MT.(ABSTRACT TRUNCATED AT 250 WORDS)
Tolloczko
B
B
Seymour Heisler Laboratory, Montreal Chest Hospital Research Center, Quebec, Canada.
Jia
Y L
YL
Martin
J G
JG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008024:Ligands; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009991:Oscillometry; D051381:Rats; D011917:Rats, Inbred Lew; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D008024:Ligands; D011985:Receptors, Serotonin; D012701:Serotonin; D000242:Cyclic AMP; D002118:Calcium