Abstract
Hexarelin, an analogue of GHRP-6, in which D-Tryptophan has been replaced by its 2-methyl derivative, is known to release growth hormone (GH) in vivo and in vitro by direct action on receptors present in anterior pituitary cells.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 Mr of 57,000 in human, bovine and porcine anterior pituitary membranes. Hexarelin and the spiroindoline sulfonamide MK-0677 displaced the Mr-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.
Citations
Mar 25, 1999·Journal of Endocrinological Investigation·E ArvatE Ghigo
Mar 3, 2001·Journal of Endocrinological Investigation·R DeghenghiG Muccioli
Feb 11, 1999·Journal of Endocrinological Investigation·R Deghenghi
Apr 9, 1999·Journal of Endocrinological Investigation·E ArvatE Ghigo
Dec 4, 2009·Chemical Biology & Drug Design·Nicolas BoutardWilliam D Lubell
Apr 4, 2006·British Journal of Pharmacology·Delphine MousseauxJean Martinez
Oct 3, 2001·Biopolymers·V TheodorouC Sakarellos
Nov 6, 2004·FEBS Letters·Chi-Bun ChanChristopher H K Cheng
Oct 26, 1999·Circulation Research·V BodartH Ong
May 4, 2002·Circulation Research·V BodartH Ong
Nov 26, 2002·Endocrinology·Shane R Cunha, Kelly E Mayo
Jan 18, 2002·Endocrinology·Corrado GhèMauro Papotti
Nov 4, 2000·The Journal of Clinical Endocrinology and Metabolism·M PapottiG Muccioli
Apr 12, 2001·The Journal of Clinical Endocrinology and Metabolism·P CassoniG Muccioli
Dec 30, 1999·Endocrinology·A TivestenJ Isgaard
Aug 28, 1999·Endocrinology·V LocatelliF Berti
Sep 10, 2003·Endocrinology·María M MalagónJusto P Castaño
Apr 1, 2009·Future Medicinal Chemistry·Luca Costantino, Daniela Barlocco
Aug 24, 2001·Molecular Endocrinology·A GarcíaC Diéguez
Jan 26, 2008·Endocrinology·Inger JohanssonJörgen Isgaard
Jan 27, 1999·The Journal of Clinical Endocrinology and Metabolism·E GhigoE E Müller
Dec 23, 1998·Endocrine Reviews·A Giustina, J D Veldhuis
Jun 8, 2004·Endocrine Reviews·Aart J van der LelyEzio Ghigo
May 26, 1999·Journal of Endocrinological Investigation·G BisiE Ghigo
Sep 27, 2000·Journal of Endocrinological Investigation·R Deghenghi
Sep 18, 2008·Arquivos brasileiros de endocrinologia e metabologia·Manuel H Aguiar-OliveiraAdão C Nascimento-Junior
Oct 27, 2018·Biomedicines·Stéphane TurcotteWilliam D Lubell
Jul 13, 1999·Journal of Endocrinological Investigation·G GuzzaloniF Morabito
Apr 30, 1999·Physiological Reviews·E E MüllerD Cocchi
Jun 5, 2004·The Biochemical Journal·Annie DemersHuy Ong
Apr 18, 2003·Clinical Endocrinology·J SvenssonUNKNOWN NN703 Clinical Research Group
May 21, 2009·Journal of the American Chemical Society·Andrew G JamiesonWilliam D Lubell
Jun 24, 2021·Journal of Medicinal Chemistry·Ragnhild G OhmWilliam D Lubell
Oct 14, 2017·Journal of Medicinal Chemistry·Kelvine Chignen PossiWilliam D Lubell
Jun 23, 2011·Journal of the American Chemical Society·David SabatinoWilliam D Lubell