title: Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular smooth muscle cells in culture.
abstract: Cultured smooth muscle cells obtained from rat lung periphery (RPC) and proximal pulmonary artery (RSMC) expressed mRNA for serotonin (5-HT) type 2 receptor (5-HT2) and 5-HT transporter (by Northern blot analysis). Functional expression of these genes was evident since both cell types 1) bound 125I-labeled lysergic acid diethylamide (LSD; 5-HT2 receptor antagonist) that was equally effectively displaced by either ketanserin or mianserin; and 2) transported 5-[3H]HT in an imipramine-sensitive manner. Serotonin (10(-9)-10(-5) M) stimulated DNA synthesis (as measured by [3H]thymidine uptake) in RPC and RSMC. The 5-HT-induced increase in DNA synthesis was significantly inhibited in both cell types by the 5-HT2 receptor antagonist, ketanserin (10(-7)-10(-6) M), and by fluoxetine (10(-6) M), a putative 5-HT transport inhibitor. Acute exposure to 5-HT (1-100 microM) caused an abrupt rise in intracellular calcium ([Ca2+]i) in single pulmonary vascular smooth muscle cells as microspectrofluorometrically determined using the calcium-sensitive dye, fura 2. The 5-HT-induced change in [Ca2+]i was completely abolished in the presence of 10(-6) M ketanserin as well as imipramine or fluoxetine (10(-6) M). The calcium transients due to 5-HT persisted in a Na(+)-free condition (in which the transporter activity was completely abolished) and imipramine and fluoxetine (and ketanserin) were effective inhibitors of 5-HT under these conditions. Therefore, the 5-HT2 receptor, but not the transporter, is responsible for initiating the acute effects (e.g., calcium transients) of 5-HT in cultured rat pulmonary vascular smooth muscle cells and fluoxetine (1 microM) may have 5-HT2-receptor antagonist properties.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
authors.forename: B R
authors.initials: BR
authors.lastname: Pitt
authors.forename: W
authors.initials: W
authors.lastname: Weng
authors.forename: A R
authors.initials: AR
authors.lastname: Steve
authors.forename: R D
authors.initials: RD
authors.lastname: Blakely
authors.forename: I
authors.initials: I
authors.lastname: Reynolds
authors.forename: P
authors.initials: P
authors.lastname: Davies
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D007650:Ketanserin / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000378:metabolism; D008803:Mianserin / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics; D012701:Serotonin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin; D008803:Mianserin; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D004247:DNA; D007650:Ketanserin; D002118:Calcium; D013936:Thymidine