MOLECULAR-CLONING, CHARACTERIZATION, AND LOCALIZATION OF A HIGH-AFFINITY SEROTONIN RECEPTOR (5-HT(7)) ACTIVATING CAMP FORMATION

被引:576
作者
RUAT, M [1 ]
TRAIFFORT, E [1 ]
LEURS, R [1 ]
TARDIVELLACOMBE, J [1 ]
DIAZ, J [1 ]
ARRANG, JM [1 ]
SCHWARTZ, JC [1 ]
机构
[1] UNIV PARIS 05,FAC PHARM,PHYSIOL LAB,F-75270 PARIS 06,FRANCE
关键词
RAT; CHINESE HAMSTER OVARY CELLS; IN-SITU HYBRIDIZATION;
D O I
10.1073/pnas.90.18.8547
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
By using a strategy based on nucleotide sequence homology, we have cloned a cDNA encoding a functional serotonin (5-HT) receptor. The deduced amino acid sequence of the 5-HT7 receptor displays limited homology with that of other 5-HT receptors. In addition to the seven stretches of hydrophobic amino acids that characterize the superfamily of receptors interacting with guanine nucleotide-binding proteins, the 448-aa sequence of the 5-HT7 receptor contains a hydrophobic domain located at its N-terminal end. Genomic analysis indicated the presence of introns interrupting the coding sequence. The 5-HT7 receptor, stably expressed in transfected CHO cells, bound [H-3]5-HT with high affinity (K(d) = 1 nM), like receptors of the 5-HT1 subfamily from which, however, it was clearly distinguished by its pharmacology. 5-HT in nanomolar concentrations stimulated cAMP accumulation in these CHO cells by almost-equal-to 10-fold, whereas lysergic acid diethylamide displayed low intrinsic agonist activity. These various properties differentiate the 5-HT7 receptor from the four other subfamilies of mammalian 5-HT receptors (i.e., the 5-HT1-, 5-HT2-, 5-HT3-, and 5-HT4-like subfamilies) and, therefore, appear to define another receptor subfamily. Northern blot and in situ hybridization analyses showed the 5-HT7 transcripts to be expressed in discrete areas of the limbic brain (e.g., pyramidal hippocampus cells, tenia tecta, amygdaloid, or mammillary nuclei), suggesting that the receptor mediates serotoninergic controls in functions like mood, learning, or neuroendocrine and vegetative behaviors.
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页码:8547 / 8551
页数:5
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