CHARACTERIZATION OF GALANIN AND 5-HT1A RECEPTOR COUPLING TO ADENYLYL-CYCLASE IN DISCRETE REGIONS OF THE RAT-BRAIN

被引:19
作者
BILLECOCQ, A
HEDLUND, PB
BOLANOSJIMENEZ, F
FILLION, G
机构
[1] INST PASTEUR,NEUROIMMUNOENDOCRINOL PHARMACOL UNIT,PARIS,FRANCE
[2] KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1994年 / 269卷 / 02期
关键词
GALANIN; 5-HT; (5-HYDROXYTRYPTAMINE; SEROTONIN); 8-OH-DPAT (8-OH-2-(DI-N-PROPYLAMINO)-TETRALIN); ADENYLYL CYCLASE; FORSKOLIN; HYPOTHALAMUS; HIPPOCAMPUS; BRAIN; RECEPTOR SUBTYPE; PEPTIDE FRAGMENT;
D O I
10.1016/0922-4106(94)90088-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have studied the coupling of galanin and 5-HT1A receptors with adenylyl cyclase in the hypothalamus, the entorhinal cortex and the hippocampus of the rat brain. Furthermore, we have evaluated the effects of simultaneous activation of galanin and 5-HT1A receptors on adenylyl cyclase activity. Galanin-(1-29) and galanin-(1-15) showed a dose-dependent inhibitory effect on forskolin-stimulated adenylyl cyclase activity in the hypothalamus and entorhinal cortex. No clear effects were observed in the hippocampus. Neither galanin-(1-29) nor galanin-(1-15) had any effect on the basal activity of adenylyl cyclase in these regions. The selective 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tetralin (8-OH-DPAT) induced a dose-dependent inhibition of forskolin stimulated adenylyl cyclase activity in the hippocampus and the entorhinal cortex. 5-HT induced an inhibition in the hypothalamus. In all regions the effects could be fully counteracted by methiothepin. 5-HT was shown to stimulate the basal activity of adenylyl cyclase in the hippocampus and the entorhinal cortex. The effects could be counteracted by methiothepin. When galanin-(1-29) and 5-HT/8-OH-DPAT were incubated simultaneously additive inhibitory effects, but no synergistic interactions, could be observed on the stimulated adenylyl cyclase activity. In conclusion, galanin and 5-HT1A receptors seem to be linked to different independent pools of G proteins, indicating that the previously demonstrated intramembrane interactions between galanin and 5-HT1A receptors involve a mechanism not directly related to adenylyl cyclase.
引用
收藏
页码:209 / 217
页数:9
相关论文
共 53 条
[1]   MECHANISM OF GALANIN-INHIBITED INSULIN RELEASE - OCCURRENCE OF A PERTUSSIS-TOXIN-SENSITIVE INHIBITION OF ADENYLATE-CYCLASE [J].
AMIRANOFF, B ;
LORINET, AM ;
LAGNYPOURMIR, I ;
LABURTHE, M .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1988, 177 (01) :147-152
[2]   SEROTONIN-ELICITED AMPLIFICATION OF ADENYLATE-CYCLASE ACTIVITY IN HIPPOCAMPAL MEMBRANES FROM ADULT-RAT [J].
BARBACCIA, ML ;
BRUNELLO, N ;
CHUANG, DM ;
COSTA, E .
JOURNAL OF NEUROCHEMISTRY, 1983, 40 (06) :1671-1679
[3]  
BARD JA, 1993, J BIOL CHEM, V268, P23422
[4]   GALANIN AND GALANIN ANTAGONISTS - MOLECULAR AND BIOCHEMICAL PERSPECTIVES [J].
BARTFAI, T ;
FISONE, G ;
LANGEL, U .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1992, 13 (08) :312-317
[5]  
BARTFAI T, 1993, CRIT REV NEUROBIOL, V7, P229
[6]  
BOCKAERT J, 1987, N-S ARCH PHARMACOL, V335, P588
[7]   GALANIN INHIBITS ADENYLATE-CYCLASE OF RAT-BRAIN MEMBRANES [J].
CHEN, YH ;
LABURTHE, M ;
AMIRANOFF, B .
PEPTIDES, 1992, 13 (02) :339-341
[8]  
DEVIVO M, 1986, J PHARMACOL EXP THER, V238, P248
[9]  
DUMUIS A, 1988, MOL PHARMACOL, V33, P178
[10]   REVERSED-PHASE LIQUID-CHROMATOGRAPHIC DETERMINATION OF CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE IN RAT-BRAIN CORTEX [J].
FAYOLLE, C ;
FILLION, G .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1988, 426 (01) :177-182