Skip to main content

Physiological Function of Growth Hormone Secretagogue Receptors in the Cardiovascular System

  • Conference paper
Peptides and Non Peptides of Oncologic and Neuroendocrine Relevance
  • 60 Accesses

Abstract

Growth hormone secretagogues (GHS) consist of a series of small enkephalin derived peptides identified as growth hormone-releasing peptides (GHRPs) (Bowers, 1993) and non-peptidyl derivatives modeled from GHRPs (Smith et al., 1997). To this class of compounds is recently added a new member, ghrelin, an endogenous 28 amino acid polypeptide isolated from the stomach (Kojima et al., 1999). GHS share a common activity in stimulating the release of growth hormone (GH) from the pituitary in several animal species and in man (Ghigo et al., 2001). The GH release is mediated through the binding of GHS to a G protein-coupled receptor identified by expression cloning as GHS-Ria or ghrelin receptor, for which mRNA expression as well as protein receptor localization are mainly confined to the hypothalamus and the pituitary (Howard et al., 1996).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bedendi I., Gallo M.P., Malan D., Levi R.C. and Alloatti G. (2001). Role of endothelial cells in modulation of contractility induced by hexarelin in rat ventricle. Life Sci, 69, 2189–2201.

    Article  PubMed  CAS  Google Scholar 

  • Berti F., Rossoni G., and De Gennaro Colonna V. (1999). Hexarelin, a synthetic growth hormone secretagogue, exhibits protectant activity in experimental myocardial ischemia and reperfusion. In Growth hormone secretagogues, eds E. Ghigo, M. Boghen, F.F. Casanueva and C. Dieguez, pp. 301–314. New York, Elsevier Science.

    Chapter  Google Scholar 

  • Bisi G., Podio V.,Valetto M.R., Broglio F., Bertuccio G., Del Rio G.,Arvat E., Boghen M.F., Deghenghi R., Muccioli G.,Ong H. and Ghigo E. (1999). Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest, 22, 266–272.

    CAS  Google Scholar 

  • Bodart V., Bouchard J.F., McNicoll N., Escher E., Carriere P., Ghigo E., Sejlitz T., Sirois M.G., Lamontagne D. and Ong, H. (1999). Identification and characterization of a new growth hormone-releasing peptide receptor in the heart. Circ Res, 85, 796–802.

    Article  PubMed  CAS  Google Scholar 

  • Bodart V., Febbraio M., Demers A., McNicoll N., Pohankova P., Perreault A., Sejlitz T., Escher E., Silverstein R.L., Lamontagne D. and Ong, H. (2002). CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res, 90, 844–849

    Article  PubMed  CAS  Google Scholar 

  • Bouchard J.F. and Lamontagne D. (1996). Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury. Am J Physiol, 271, H1801–H186.

    PubMed  CAS  Google Scholar 

  • Bowers C.Y. (1993). GH-releasing peptides-structure and kinetics. J Pediatr Endocrinol, 6, 21–31.

    Article  PubMed  CAS  Google Scholar 

  • Cassoni P., Papotti M., Ghè C., Catapano F., Sapino A., Graziani A., Deghenghi R., Reissmann T., Ghigo E. and Muccioli G. (2001). Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab, 86, 1738–1745.

    Article  PubMed  CAS  Google Scholar 

  • Date Y., Nakazato M., Hashiguchi S., Dezaki K., Mondal M.S., Hosoda H., Kojima M., Kangawa K.,Arima T., Matsuo H., Yada T.and Matsukura S. (2002). Ghrelin is present in pancreatic a-cells of humans and rats and stimulates insulin secretion. Diabetes, 51, 124–129.

    CAS  Google Scholar 

  • De Gennaro Colonna V., Rossoni G., Bernareggi M., Muller E.E. and Berti F. (1997). Cardiac ischemia and impairment of vascular endothelium function in hearts from growth hormone-deficient rats: protection by hexarelin. Eur J Pharmacol, 334, 201–207.

    Article  PubMed  CAS  Google Scholar 

  • De Gennaro Colonna V., Rossoni G., Cocchi D., Rigamonti A.E., Berti F.and Muller E.E. (2000). Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats. J Endocrinol, 166, 529–536.

    Article  PubMed  CAS  Google Scholar 

  • Febbraio M., Hajjar D.P., and Silverstein R.L. (2001). CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest, 108, 785–791.

    PubMed  CAS  Google Scholar 

  • Filigheddu N., Fubini A., Baldanzi G., Cutrupi S., Ghe C., Catapano F., Broglio F., Bosia A., Papotti M., Muccioli G., Ghigo E., Deghenghi R. and Graziani A. (2001). Hexarelin protects H9c2 cardiomyocytes from doxorubicin-induced cell death. Endocrine, 14, 113–119

    Article  PubMed  CAS  Google Scholar 

  • Ghigo E., Arvat E., Giordano R., Broglio F.,Gianotti L., Maccario M., Bisi G., Graziani A., Papotti M., Muccioli G., Deghenghi R. and Camanni F. (2001). Biologic activ ities of growth hormone secretagogues in humans. Endocrine, 14, 87–93.

    CAS  Google Scholar 

  • Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B., and Korbonits M. (2002). The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab, 87, 2988.

    Article  PubMed  CAS  Google Scholar 

  • Hattori N., Saito T., Yagyu T., Jiang B.-H., Kitagawa K., and Inagaki C. (2001). GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab, 86, 4284–4291.

    Article  PubMed  CAS  Google Scholar 

  • Howard A.D., Feighner S., Cully D.F., Arena J.P., Liberator P.A., Resenblum C.I., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C, Chou M., Liu K.K., McKee K.K., Pong S.S., Chaung L.Y., Elbrecht A., Dashkevicz M., Heavens R., Rigby M., Sirinathsinghji D.J., Dean D.C., Mellilo D.G. and Van der Ploeg L.H. (1996). A receptor in pituitary and hypothalamus that functions in growth hormone release. Science, 273, 974–977

    Article  PubMed  CAS  Google Scholar 

  • Katugampola S.D., Pallikaros Z. and Davenport M. (2001). 125I-His(9)-ghrelin, a novel radiologand for localizing GHS orphan receptors in human and rat tissue: up-regula-tion of receptors with atherosclerosis. Br J Pharmacol, 134, 143–149.

    Article  PubMed  CAS  Google Scholar 

  • Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H. and Kangawa K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402, 656–660.

    Article  PubMed  CAS  Google Scholar 

  • Locatelli V., Rossoni G., Schweiger R, Torsello A., De Gennaro C.V., Bernareggi M., Deghenghi R., Muller E.E. and Berti F. (1999). Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology, 140, 4024–4031.

    Article  PubMed  CAS  Google Scholar 

  • MacAndrew J.T., Ellery S.S., Parry M.A., Pan L.C. and Black S.C. (2001). Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury. Eur J Pharmacol, 432, 195–202.

    Article  PubMed  CAS  Google Scholar 

  • Muccioli G., Broglio F., Valetto M.R., Ghè C, Catapano F., Graziani A., Papotti M., Bisi G., Deghenghi R. and Ghigo E. (2000). Growth hormone-releasing peptides and the cardiovascular system. Ann Endocrinol, 61, 27–31.

    CAS  Google Scholar 

  • Musters R.J., van der Meulen E.T., Zuidwijk M., Muller A., Simonides W.S., Banerjee A. and van Hardeveld C. (1999). PKC-dependent preconditionning with norepinephrine protects sarcoplasmic reticulum function in rat trabeculae following metabolic inhibition. J Mol Cell Cardiol, 31, 1083–1094.

    Article  CAS  Google Scholar 

  • Nagaya N., Kojima M., Uematsu M., Yamagishi M., Hosoda H., Oya H., Hayashi Y. and Kangawa K. (2001). Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regulatory Integrative Comp Physiol, 280, R1483–R1487.

    CAS  Google Scholar 

  • Okumura H., Nagaya N., Enomoto M., Nakagawa E., Oya H. and Kangawa K. (2002). Vasodilatory effect of ghrelin and endogenous peptides from the stomach. J Cardiovasc Pharmacol, 39, 779–783.

    Article  PubMed  CAS  Google Scholar 

  • Ong H., Bodart V, McNicoll N., Lamontagne D. and Bouchard J.E (1998a). Binding sites for growth hormone-releasing peptide. Growth Horm IGF Res, 8 (Suppl B), 137–140.

    Article  Google Scholar 

  • Ong H, McNicoll N., Escher E., Collu R., Deghenghi R., Locatelli V, Ghigo E., Muccioli G., Boghen M. and Nilsson A. (1998b). Identification of a pituitary growth hormone-releasing peptide (GHRP) receptor subtype by photoaffmity labeling. Endocrinology, 139, 432–435.

    Article  Google Scholar 

  • Papotti M., Ghè C, Cassoni P., Catapano F., Deghenghi R., Ghigo E. and Muccioli G. (2000). Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab, 85, 3803–3807.

    Article  PubMed  CAS  Google Scholar 

  • Rossoni G., De Gennaro Colonna V., Bernareggi M., Polvani G.L., Muller E.E. and Berti F. (1998). Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats. J Cardiovasc Phamacol, 32, 260–265.

    Article  CAS  Google Scholar 

  • Smith R.G., Van der Ploeg L.H.T., Howard A.D., Feighner S.D., Cheng K., Hickey G.J., Wyvratt M.J. Jr, Fisher M.H., Nargund R.P. and Patchett A.A. (1997). Peptidomimetic regulation of growth hormone secretion. Endoc Rev, 18, 621–645.

    Article  CAS  Google Scholar 

  • Tivesten Ã…., Bollano E., Caidahl K., Kujacic V, Sun X.Y., Hedner T., Hjalmarson Ã…., Bengtsson B.-Ã…. and Isgaard J. (2000). The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology, 141, 60–66.

    Article  PubMed  CAS  Google Scholar 

  • Tschöp M., Smiley D.L. and Heiman M.L. (2000). Ghrelin induces adiposity in rodents. Nature, 407,908–913.

    Article  PubMed  Google Scholar 

  • Weekers R, Van Herck E., Isgaard J. and Van den Berghe G. (2000). Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model. Endocrinology, 141, 3993–3999.

    Article  PubMed  CAS  Google Scholar 

  • Wiley K.E. and Davenport A.P. (2002). Comparison of vasodilators in human mammary arteries: ghrelin is a potent physiological antagonist of endothelin. Br J Pharmacol, 136, 1146–1152.

    Article  PubMed  CAS  Google Scholar 

  • Wren A.A., Small C.J., Abbott CR., Dhillo W.S., Seal L.J., Cohen M.A., Batterham R.L., Taheri S., Stanley S.A., Ghatei M.A. and Bloom S.R. (2001). Ghrelin causes hyperpha-gia and obesity in rats. Diabetes, 50, 2540–2547.

    Article  PubMed  CAS  Google Scholar 

  • Wu D., Clarke I.J. and Chen C. (1997). The role of protein kinase C (PKC) in growth hormone (GH) secretion induced by GH-releasing factor (GRF) and GH-releasing peptides (GHRP) in cultured ovine somatotrophs. J Endocrinol, 154, 219–230.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Italia

About this paper

Cite this paper

Ong, H., Lamontagne, D., Demers, A., Marleau, S. (2003). Physiological Function of Growth Hormone Secretagogue Receptors in the Cardiovascular System. In: Müller, E.E. (eds) Peptides and Non Peptides of Oncologic and Neuroendocrine Relevance. Springer, Milano. https://doi.org/10.1007/978-88-470-2085-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-2085-6_12

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2170-9

  • Online ISBN: 978-88-470-2085-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics