Contractile effect of ghrelin on isolated guinea-pig renal arteries.
Ghrelin, a 28-amino acid peptide, known to exist in both acylated and des-acylated varieties, was identified as the first endogenous ligand of growth hormone secretagogue receptor in 1999. Various arteries are known to express ghrelin receptors, but the direct action of ghrelin on blood vessels has been unclear. In the present study we show that ghrelin concentration-dependently potentiates endothelin-1 (ET-1) induced tension development of guinea-pig renal artery, as measured using a wire-type isometric myography of vascular segments. In vascular smooth muscle cells (SMC) ghrelin caused activation of potassium outward currents via phospholipase C (PLC)-->inositol-1,4,5-trisphosphate (IP3) and PLC-->protein kinase C (PKC) signalling cascade, resulting in hyperpolarizaton of the cell membrane. On a tissue level ghrelin by itself had no effect on isometric tone, but augmented ET-1 induced contraction by a mechanism, involving PLC, Rho-kinase and intracellular IP3 -sensitive Ca2+ release, and not nucleotide-sensitive protein kinases or PKC. Together with our previous findings the data in this study suggest that ghrelin exerts its contractile activity on guinea-pig renal artery by facilitation of ET-1 triggered intracellular signalling in SMC, and/or by stimulating the release of a yet unknown contractile mediator from endothelium.
Dimitrova
Daniela Z
DZ
Institute of Biophysics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Mihov
Deyan N
DN
Wang
Rui
R
Hristov
Kiril L
KL
Rizov
Lazar I
LI
Bolton
Thomas B
TB
Duridanova
Dessislava B
DB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D054439:Ghrelin; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D036361:Peptide Hormones / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D054439:Ghrelin; D036361:Peptide Hormones; D013779:Tetrodotoxin; D002118:Calcium