Rat cerebral cortex corticotropin-releasing hormone receptors: evidence for receptor coupling to multiple G-proteins

被引:114
作者
Grammatopoulos, DK
Randeva, HS
Levine, MA
Kanellopoulou, KA
Hillhouse, EW
机构
[1] Univ Warwick, Dept Biol Sci, Sir Quinton Hazell Mol Med Res Ctr, Coventry CV4 7AL, W Midlands, England
[2] Johns Hopkins Univ, Sch Med, Div Paediat Endocrinol, Baltimore, MD USA
关键词
bacterial toxins; CRH receptor; G-proteins; rat cortex; second messengers;
D O I
10.1046/j.1471-4159.2001.00067.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The wide distribution of corticotrophin-releasing hormone (CRH) receptors in brain and periphery appear to be important in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli. The type 1 receptors are highly expressed throughout the cerebral cortex, a region involved in cognitive function and modulation of stress responses, where they are coupled to the adenylyl cyclase system. Using techniques that analyse receptor-mediated guanine-nucleotide binding protein (G-proteins) activation, we recently demonstrated that expressed type 1 alpha CRH receptors are capable of activating multiple G-proteins, which suggests that CRH can regulate multiple signalling pathways. in an effort to characterize the intracellular signals generated by CRH in the rat cerebral cortex we sought to identify G-proteins activated by CRH in a physiological membrane environment. Rat cerebral cortical membrane suspensions were analysed for the ability of CRH to stimulate incorporation of [alpha-P-32]-GTP-gamma -azidoanilide to Various G-protein alpha -chains. Our results show that CRH receptors are coupled to and activate at least five different G-proteins (Gs, Gi, Gq(/11), Go and Gz) with subsequent stimulation of at feast two intracellular signalling cascades. In addition, the photoaffinity experiments indicated that the CRH receptors preferentially activate the 45 kDa form of the Gs alpha -protein. This data may help elucidate the intracellular signalling pathways mediating the multiple actions of CRH especially under different physiological conditions.
引用
收藏
页码:509 / 519
页数:11
相关论文
共 39 条
[1]  
Ahmed AH, 1997, J CELL PHYSIOL, V170, P263, DOI 10.1002/(SICI)1097-4652(199703)170:3<263::AID-JCP7>3.0.CO
[2]  
2-M
[3]   IMMUNOREGULATORY FEEDBACK BETWEEN INTERLEUKIN-1 AND GLUCOCORTICOID HORMONES [J].
BESEDOVSKY, H ;
DELREY, A ;
SORKIN, E ;
DINARELLO, CA .
SCIENCE, 1986, 233 (4764) :652-654
[4]  
CHEN FM, 1986, BRAIN RES, V381, P49
[5]   DETERMINATION OF MASS CHANGES IN PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE AND EVIDENCE FOR AGONIST-STIMULATED METABOLISM OF INOSITOL 1,4,5-TRISPHOSPHATE IN AIRWAY SMOOTH-MUSCLE [J].
CHILVERS, ER ;
BATTY, IH ;
CHALLISS, RAJ ;
BARNES, PJ ;
NAHORSKI, SR .
BIOCHEMICAL JOURNAL, 1991, 275 :373-379
[6]  
Chrousos George P., 1998, Annals of Internal Medicine, V129, P229
[7]   Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins [J].
Fields, TA ;
Casey, PJ .
BIOCHEMICAL JOURNAL, 1997, 321 :561-571
[8]   CORTICOTROPIN-RELEASING FACTOR (CRF) - CENTRAL EFFECTS ON MEAN ARTERIAL-PRESSURE AND HEART-RATE IN RATS [J].
FISHER, LA ;
RIVIER, J ;
RIVIER, C ;
SPIESS, J ;
VALE, W ;
BROWN, MR .
ENDOCRINOLOGY, 1982, 110 (06) :2222-2224
[10]   Solubilization and biochemical characterization of the human myometrial corticotrophin-releasing hormone receptor [J].
Grammatopoulos, D ;
Hillhouse, EW .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1998, 138 (1-2) :185-198