RELATIONSHIP BETWEEN 5-HT2A RECEPTOR MESSENGER-RNA DENSITY AND CONTRACTILITY IN TRACHEA AND AORTA FROM GUINEA-PIG AND RAT

The present studies document marked differences in contractile respons iveness to serotonin in trachea and aorta between guinea pig and rat. For example, the guinea pig trachea and rat aorta markedly contract in response to serotonin via activation of 5-HT2A receptors. In contrast , the rat trachea and guinea pig aorta only modestly contract to serot onin. The availability of 5-HT2A receptor selective cDNA clones from b rain of both guinea pig and rat permitted molecular probes to be desig ned and PCR amplification studies initiated to identify and quantify 5 -HT2A receptor specific mRNA in these tissues. For trachea, 3-fold hig her concentrations of 5-HT2A receptor specific mRNA were found in guin ea pig relative to rat trachea. These data are consistent with the mor e profound contractile response to serotonin in guinea pig versus rat trachea and suggest that differences in tracheal contractility to sero tonin correlate with the density of 5-HT2A receptor mRNA. In contrast, although rat aorta contracted more dramatically to serotonin than gui nea pig aorta, rat aorta possessed a similar concentration of 5-HT2A r eceptor specific mRNA as compared to guinea pig aorta. Thus, for the a orta, differences in the concentration of 5-HT2A receptor mRNA are not sufficient to explain the observed differences in contractility betwe en tissues from guinea pig and rat. These studies documenting 5HT(2A) receptor mRNA in rat trachea and guinea pig aorta, two tissues that do not markedly contract in response to serotonin indicate that 5-HT2A r eceptor mRNA although present, has not resulted in a receptor capable of mediating a contractile response in these tissues.