Identification of a pituitary growth hormone-releasing peptide (GHRP) receptor subtype by photoaffinity labeling

被引:94
作者
Ong, H [1 ]
McNicoll, N
Escher, E
Collu, R
Deghenghi, R
Locatelli, V
Ghigo, E
Muccioli, G
Boghen, M
Nilsson, M
机构
[1] Univ Montreal, Fac Pharm, Montreal, PQ, Canada
[2] Univ Montreal, Ste Justine Hosp, Montreal, PQ, Canada
[3] Univ Sherbrooke, Dept Pharmacol, Sherbrooke, PQ J1K 2R1, Canada
[4] Europeptides, Argenteuil, France
[5] Univ Milan, Dept Pharmacol, Milan, Italy
[6] Univ Turin, Dept Internal Med, Turin, Italy
[7] Univ Turin, Dept Anat, Turin, Italy
[8] Pharmacia & Upjohn Inc, Stockholm, Sweden
关键词
D O I
10.1210/en.139.1.432
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Hexarelin, an analogue of GHRP-6, in which D-Tryptophan has been replaced by its 2-methyl derivative, is known to release growth hormone (GH) in vivo and in vitro by direct action on receptors present in anterior pituitary cells. Measurement of second messengers (c-AMP, Ca++, IP3) upon somatotrophs stimulation, suggests the existence of more than one GHRP receptor subtype. In order to document such an hypothesis, we have used a new photoactivatable derivative of Hexarelin, Tyr-Bpa-Ala-Hexarelin. This derivative was shown to be fully active in the release of GH in vivo with neonate rats. Using this photoactivatable ligand, we have specifically labeled a protein with an apparent M-r of 57 000 in human, bovine and porcine anterior pituitary membranes. Hexarelin and the spiroindoline sulfonamide MK-0677 displaced the M-r-57 000 photolabeled band with an apparent ED50 of 6x10(-7) M and 2x10(-5) M respectively. Taking into account the high efficiency (>60%) of covalent incorporation of the Bpa residue, this photoactivatable Hexarelin derivative has allowed the identification of a pituitary GHRP receptor subtype, which is apparently distinct from the recently cloned GH secretagogue receptor.
引用
收藏
页码:432 / 435
页数:4
相关论文
共 22 条
[1]   ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE [J].
BOWERS, CY ;
MOMANY, FA ;
REYNOLDS, GA ;
HONG, A .
ENDOCRINOLOGY, 1984, 114 (05) :1537-1545
[2]   STRUCTURE-ACTIVITY-RELATIONSHIPS OF A SYNTHETIC PENTAPEPTIDE THAT SPECIFICALLY RELEASES GROWTH-HORMONE INVITRO [J].
BOWERS, CY ;
MOMANY, F ;
REYNOLDS, GA ;
CHANG, D ;
HONG, A ;
CHANG, K .
ENDOCRINOLOGY, 1980, 106 (03) :663-667
[3]   STIMULATION OF GROWTH-HORMONE RELEASE FROM RAT PRIMARY PITUITARY-CELLS BY L-692,429, A NOVEL NON-PEPTIDYL GH SECRETAGOGUE [J].
CHENG, K ;
CHAN, WWS ;
BUTLER, B ;
WEI, LT ;
SCHOEN, WR ;
WYVRATT, MJ ;
FISHER, MH ;
SMITH, RG .
ENDOCRINOLOGY, 1993, 132 (06) :2729-2731
[4]   STIMULATORY EFFECT OF THYROID-HORMONE ON GROWTH-HORMONE GENE-EXPRESSION IN A HUMAN PITUITARY CELL-LINE [J].
CHOMCZYNSKI, P ;
SOSZYNSKI, P ;
FROHMAN, LA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 77 (01) :281-285
[5]   BINDING OF A GROWTH-HORMONE RELEASING HEXAPEPTIDE TO SPECIFIC HYPOTHALAMIC AND PITUITARY BINDING-SITES [J].
CODD, EE ;
SHU, AYL ;
WALKER, RF .
NEUROPHARMACOLOGY, 1989, 28 (10) :1139-1144
[6]   BINDING OF GROWTH HORMONE-RELEASING HORMONES AND ENKEPHALIN-DERIVED GROWTH HORMONE-RELEASING PEPTIDES TO MU-OPIOID AND DELTA-OPIOID RECEPTORS IN FOREBRAIN OF RAT [J].
CODD, EE ;
YELLIN, T ;
WALKER, RF .
NEUROPHARMACOLOGY, 1988, 27 (10) :1019-1025
[7]   BENZOPHENONE PHOTOPHORES IN BIOCHEMISTRY [J].
DORMAN, G ;
PRESTWICH, GD .
BIOCHEMISTRY, 1994, 33 (19) :5661-5673
[8]  
HOWRAD AD, 1996, SCIENCE, V273, P974
[9]  
IMBIMBO BP, 1994, EUR J CLIN PHARMACOL, V46, P421
[10]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+