Functional characterization of serotonin receptors in rat isolated aorta.
Interactions of serotonin (5-HT) with different specific 5-HT receptors that can coexist in the same blood vessel sometimes generate opposite effects. The aim of this study was to characterize the functional role of previously described mRNAs for 5-HT receptors in the rat aorta (5-HT(2A), 5-HT(2B), 5-HT(1B), 5-HT(7)) as well as to study the known 5-HT(2A) receptor-mediated constrictor response and investigate the influences of endothelium and preconstriction on the tissue in that response. A slight endothelium- and concentration-dependent relaxant effect was observed for 5-HT in aorta precontracted with either 5 microM phenylephrine (PE) or 1 microM prostaglandin F2alpha (PGF2alpha) in the presence of 0.3 microM ketanserin. EC50 values for 5-HT and alpha-methyl-5-HT relaxant responses after PE were 43.10 +/- 4.00 and 57.11 +/- 8.01 nM, respectively. pK(B) values for antagonists cyproheptadine and rauwolscine were 8.92 +/- 0.22 and 7.15 +/- 0.12, respectively. In nonprecontracted tissues, the contractile potency of 5-HT was higher in the absence of endothelium (EC50, degreesM): 2.60 +/- 0.28 and 4.12 +/- 0.21 in the absence and in the presence of endothelium, respectively. The differences were statistically significant (p<0.05). In precontracted tissues, the differences in EC50 values (2.22 +/- 0.40 and 4.65 +/- 0.60 microM without and with endothelium, respectively) were also statistically significant (p<0.05). pK(B) values for the 5-HT(2A) antagonist ketanserin were similar under all conditions tested. In conclusion, under our experimental conditions there are two functional 5-HT receptors in rat aorta: 5-HT(2A) contractile receptor in smooth muscle and a high-affinity relaxant receptor that mediates a very slight response and the pharmacology of which could be compatible with an endothelial 5-HT(2B) receptor.
Villazón
María
M
Department of Pharmacology, School of Pharmacy, A Coruña, Spain.
Padín
Juan Fernando
JF
Cadavid
María Isabel
MI
Enguix
María José
MJ
Tristán
Helena
H
Orallo
Francisco
F
Loza
María Isabel
MI
D000465:Algorithms; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D003533:Cyproheptadine / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D007650:Ketanserin; D015237:Dinoprost