Ghrelin signaling in human mesenteric arteries

• Autorzy: Dimitrova D. Z. , Dimitrov S.D. , Iliev I. , Mladenov M.I. , Hristov K.L. , Mihov D.N. , Duridanova D.B. , Gagov H.S.
• Języki publikacji: EN

Abstrakty

EN

The hypothesis is that the ghrelin signal pathway consists of new participants including a local second mediator in human mesenteric arteries. The contractile force of isometric artery preparations was measured using a wire-myograph. Whole-cell patch clamp experiments were performed on freshly isolated single smooth muscle cells from the same tissue. After the addition of ghrelin (100 nmol) the outward potassium currents conducted through iberiotoxin-sensitive calcium-activated potassium channels with a large conductance were almost entirely abolished. The effect of ghrelin on potassium currents was insensitive to selective inhibitors of cAMP-dependent protein kinase and soluble guanylate cyclase, but was eliminated in the presence of des-octanoyl ghrelin and O-(octahydro-4,7-methano-1H-inden-5-yl) carbonopotassium dithioate (D-609). Ghrelin dose-dependently increased the force of contraction of native, endothelium-denuded and mostly of endothelium-denuded and treated with tetrodotoxin human mesenteric arteries preconstricted with 1 nmol endothelin-1. This effect of ghrelin was blocked when the bath solution contained 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), D-609, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203x), pertussis toxin, 2-aminoethyl diphenylborinate (2-APB), indomethacin, (5Z,13E)-(9S,11S,15R)-9,15,Dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20,pentanor-5,13-prostadienoic acid (AL-8810) - a non-selective prostanoid receptor antagonist, 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazolo (SC-560) - a selective cyclooxygenase 1 inhibitor, ozagrel - a selective thromboxane A2 synthase inhibitor or T prostanoid receptor antagonist GR32191B. It is concluded that ghrelin increases the force of contraction of human mesenteric arteries by a novel mechanism that involves Src kinase, mitogen-activated protein kinase kinase (MEK), cyclooxygenase 1 and T prostanoid receptor agonist, most probably thromboxane A2.

Słowa kluczowe

EN

ghrelin; signalling; man; mesenteric artery; patch clamp; smooth muscle; potassium; cAMP-dependent protein kinase; soluble guanylate cyclase; hormone; prostaglandin; thromboxane

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 4
• Opis fizyczny: p.383-390,fig.,ref.

Twórcy

autor

Dimitrova D. Z.

• Bulgarian Academy of Sciences, Sofia, Bulgaria

autor

Dimitrov S.D.

autor

Iliev I.

autor

Mladenov M.I.

autor

Hristov K.L.

autor

Mihov D.N.

autor

Duridanova D.B.

autor

Gagov H.S.

Bibliografia

• Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660.
• Davenport AP, Bonner TI, Foord SM, et al. International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol Rev 2005; 57: 541-546.
• Rossi F, Castelli A, Bianco MJ, Bertone C, Brama M, Santiemma V. Ghrelin induces proliferation in human aortic endothelial cells via ERK1/2 and PI3K/Akt activation. Peptides 2008; 29: 2046-2051.
• Rossi F, Castelli A, Bianco MJ, Bertone C, Brama M, Santiemma V. Ghrelin inhibits contraction and proliferation of human aortic smooth muscle cells by cAMP/PKA pathway activation. Atherosclerosis 2009; 203: 97-104.
• Wang Y, Nishi M, Doi A, et al. Ghrelin inhibits insulin secretion through the AMPK-UCP2 pathway in beta cells. FEBS Lett 2010; 584: 1503-1508.
• Han XF, Zhu YL, Hernandez M, Keating DJ, Chen C. Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways. Endocrine 2005; 28: 217-224.
• Ahluwalia A, Li A, Cheng G, Deng X, Tarnawski AS. Reduced ghrelin in endothelial cells plays important mechanistic role in aging-related impairment of angiogenesis. J Physiol Pharmacol 2009; 60: 29-34.
• Camina JP, Lodeiro M, Ischenko O, Martini AC, Cassanueva FF. Stimulation by ghrelin of p42/p44 mitogen-activated protein kinase through the GHS-R1a receptor: role of G-proteins and beta-arrestins. J Cell Physiol 2007; 213: 187-200.
• Brzozowski T, Konturek PC, Sliwowski Z, et. al. Prostaglandin/cyclooxygenase pathway in ghrelin-induced gastroprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther 2006; 319: 477-487.
• Konturek PC, Brzozowski T, Engel M, et al. Ghrelin ameliorates colonic inflammation. Role of nitric oxide and sensory nerves. J Physiol Pharmacol 2009; 60: 41-47.
• Nagaya N., Kojima M, Uematsu M, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 2001; 280: R1483-R1487.
• Wiley K, Davenport A. Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol 2002; 136: 1146-1152.
• Kleinz MJ, Maguire JJ, Skepper JN, Davenport AP. Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man. Cardiovasc Res 2006; 69: 227-235.
• Dimitrova DZ. Contractile effect of ghrelin on isolated human mesenteric arteries. Compt Rend Acad Bulg Sci 2006; 59: 853-858.
• Mladenov, M, Hristov, K, Duridanova, D. Ghrelin suppression of potassium currents in smooth muscle cells of human mesenteric artery. Gen Physiol Biophys 2006; 25: 333-338.
• Li A, Cheng G, Zhu GH, Tarnawski AS. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: implications beyond GH release. Biochem Biophys Res Commun 2007; 353: 238-243.
• Mladenov M, Hristov K, Dimitriova DZ, et al. Ghrelin signalling in guinea-pig femoral artery smooth muscle cells. Acta Physiol (Oxf) 2008; 194, 195-206.
• Griffin BW, Klimko P, Crider JY, Sharif NA. AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor. J Pharmacol Exp Ther 1999; 290: 1278-1284.
• Muccioli G, Baragli A, Granata R, Papotti M, Ghigo E. Heterogeneity of ghrelin/growth hormone secretagogue receptors. Toward the understanding of the molecular identity of novel ghrelin/GHS receptors. Neuroendocrinology 2007; 86: 147-164.
• Harnett KM, Cao W, Biancani P. Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles. Am J Physiol Gastrointest Liver Physiol 2005; 288: G407-G416.
• Kohno D, Gao HZ, Muroya S, Kikuyama S, Yada T. Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 2003; 52: 948-956.
• Schubert R, Nelson MT. Protein kinases: tuners of the BKCa channel in smooth muscle. Trends Pharmacol Sci 2001; 22: 505-512.
• Dezaki K, Kakei M, Yada T. Ghrelin uses Gai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells: novel signal transduction of ghrelin. Diabetes 2007; 56: 2319-2327.
• Wellman GC, Nelson MT. Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels. Cell Calcium 2003; 34: 211-212.
• Vidulescu C, Mironneau J, Mironneau C, Popescu LM. Messenger molecules of the phospholipase signaling system have dual effects on vascular smooth muscle contraction. J Cell Mol Med 2000; 4: 196-206.
• Lefkowitz RJ, Pierce KL, Luttrell LM. Dancing with different partners: protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G protein-coupling specificity. Mol Pharmacol 2002; 62: 971-974.
• Anfuso CD, Lupo G, Romeo L, et al. Endothelial cell-pericyte cocultures induce PLA2 protein expression through activation of PKCalpha and the MAPK/ERK cascade. J Lipid Res 2007; 48: 782-793.
• Norman SJ, Poyser NL. Effects of inhibitors of arachidonic acid turnover on the production of prostaglandins by the guinea-pig uterus. J Reprod Fertil 2000; 118: 181-186.
• Vysniauskiene I, Allemann R, Flammer J, Haefliger IO. Vasoactive responses of U46619, PGF2a, latanoprost, and travoprost in isolated porcine ciliary arteries. Invest Ophthalmol Vis Sci 2006; 47: 295-298.
• Ishitsuka Y, Moriuchi H, Isohama Y, et al. A selective thromboxane A2 (TXA2) synthase inhibitor, ozagrel, attenuates lung injury and decreases monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in oleic acid-induced lung injury in guinea pigs. J Pharmacol Sci 2009; 111: 211-215.
• Walch L, de Montpreville V, Brink C, Norel X. Prostanoid EP(1)- and TP-receptors involved in the contraction of human pulmonary veins. Br J Pharmacol 2001; 134: 1671-1678.
• Chow KB, Leung PK, Cheng CH, Cheung WT, Wise H. The constitutive activity of ghrelin receptors is decreased by co-expression with vasoactive prostanoid receptors when over-expressed in human embryonic kidney 293 cells. Int J Biochem Cell Biol 2008; 40: 2627-2637.
• Mousseaux D, Le Gallic L, Ryan J, et al. Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway. Br J Pharmacol 2006; 148: 350-365.
• Lodeiro M, Theodoropoulou M, Pardo M, Casanueva FF, Camina JP. c-Src regulates Akt signaling in response to ghrelin via beta-arrestin signaling-independent and -dependent mechanisms. PLoS One 2009; 4(3): e4686, doi: 10.1371/journal.pone.0004686.
• Shinde UA, Desai KM, Yu C, Gopalakrishnan V. Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin: role of calcium-activated potassium channels. J Hypertens 2005; 3(4): 79-84.
• Moazed B, Quest D, Gopalakrishnan V. Des-acyl ghrelin fragments evoke endothelium-dependent vasodilatation of rat mesenteric vascular bed via activation of potassium channels. Eur J Pharmacol 2009; 604(1-3): 79-86.
• Dimitrova DZ, Mihov DN, Wang R, et al. Contractile effect of ghrelin on isolated guinea-pig renal arteries. Vascul Pharmacol 2007; 47: 31-40.
• Pemberton CJ, Tokola H, Bagi Z, et al. Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion. Am J Physiol Heart Circ Physiol 2004; 287(4): H1522-H1529.