Skip to main content

A Weak Substance P Antagonist Inhibits L-692,585-Stimulated GH Release in Swine

  • Chapter
Growth Hormone Secretagogues

Part of the book series: Serono Symposia USA Norwell, Massachusetts ((SERONOSYMP))

  • 92 Accesses

Abstract

Growth hormone (GH) releasing hexapeptide, His-DTrp-Ala-Trp-DPhe- LysNH2 (GHRP-6), was first described as a potent GH-specific secretagogue by Bowers, et al. (2). The first described nonpeptidyl GH secretagogue, L-692,429 (3), has been shown to elicit GH release in many species including swine (4), rats (5), beagles (6), and man (7), while the more potent analogue L-692,585 has also been shown to elicit GH release in beagles (8) and swine (9). L-692,585, a novel nonpeptidyl GH secretagogue analogue of L-692,429, was found to be approximately 20-fold more potent than L-692,429 in rat pituitary cell assays (10) and in beagles in vivo (8). The GH secretagogue activity of L-692,585 has also been reported in swine (9). A weak substance P antagonist, H2N-D-Arg-Pro-Lys-Pro-D-Phe-Gln-D- Trp-Phe-D-Trp-Leu-Leu-NH2 (SPA), has been shown to inhibit GHRP-6 binding in membrane preparations of rat pituitary and hypothalamus (11) and to inhibit both GHRP-6- and L-692,429-stimulated GH responses in rat pituitary cell cultures and in rats in vivo (1). The objective of this study was to determine if SPA could inhibit the GH response elicited by L-692,585 in swine.

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 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

  1. Cheng K, Wei L, Chaung L-Y, Chan WW-S, Butler B, Pong SS, Smith RG. Substance P antagonist inhibits L-692,429-and GHRP-6-stimulated rat growth hormone release both in vitro and in vivo. Proceedings of the 76th Annual Meeting of The Endocrine Society, 1994;662(abstr).

    Google Scholar 

  2. Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 1984;114:1537–45.

    Article  PubMed  CAS  Google Scholar 

  3. Smith RG, Cheng K, Schoen WR, Pong S-S, Hickey G, Jacks T, et al. A nonpeptidyl growth hormone secretagogue. Science 1993;260:1640–3.

    Article  PubMed  CAS  Google Scholar 

  4. Chang CH, Rickes EL, McGuire L, Cosgrove S, Taylor JE, Schoen WR, et al. L-692,429, a novel non-peptidyl GH secretagogue, stimulates GH release in swine. J Anim Sci 1993;71(suppl l):P134(abstr).

    Google Scholar 

  5. Cheng K, Chan WW-S, Butler B, Wei L, Schoen WR, Wyvratt M Jr, et al. Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue. Endocrinology 1993;132:2729–31.

    Article  PubMed  CAS  Google Scholar 

  6. Hickey GJ, Jacks T, Judith F, Taylor J, Schoen WR, Krupa D, et al. Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone secretagogue, in beagles. Endocrinology 1994;134:695–701.

    Article  PubMed  CAS  Google Scholar 

  7. Gertz BJ, Barrett JS, Eisenhandler R, Krupa DA, Wittreich JM, Seibold JR, Schneider SH. Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone releasing peptide (GHRP-6). J Clin Endocrinol Metab 1993;77:1393–7.

    Article  PubMed  CAS  Google Scholar 

  8. Jacks T, Hickey G, Judith F, Taylor J, Chen H, Krupa D, Feeney W, et al. Effects of acute and repeated intravenous administration of L-692,585, a novel nonpeptidyl growth hormone secretagogue, on plasma growth hormone, ACTH, Cortisol, prolactin, thyroxin (T4), insulin and IGF-I levels in beagles. J Endocrinol 1994;143:399–406.

    Article  PubMed  CAS  Google Scholar 

  9. Hickey GJ, Baumhover J, Faidley T, Chang C, Anderson LL, Nicolich S, et al. Effect of hypothalamo-pituitary stalk transection in the pig on GH secretory activity of L-692,585. Proceedings of the 76th Annual Meeting of The Endocrine Society, 1994;366(abstr).

    Google Scholar 

  10. Schoen WR, Ok D, DeVita RJ, Pisano JM, Hodges P, Cheng K, et al. Structure- activity relationships in the amino acid sidechain of L-692,429. BioMed Chem Lett 1994;4:1117–22.

    Article  CAS  Google Scholar 

  11. Sethumadhavan K, Veeraragavan K, Bowers CY. Demonstration and characterization of the specific binding of growth hormone-releasing peptide to rat anterior pituitary and hypothalamic membranes. Biochem Biophys Res Commun 1991;178:31–7.

    Article  PubMed  CAS  Google Scholar 

  12. Desai MC, Lefkowitz SL, Thadeio PF, Longo KP, Snider RM. Discovery of a potent substance P antagonist: recognition of the key molecular determinant. J Med Chem 1992;35:4911–3.

    Article  PubMed  CAS  Google Scholar 

  13. Desai MC, Lefkowitz SL. Conformational restricted analogs of CP-99,994: synthesis of a spirocyclic amine. 1993;3 (10):2083–6.

    CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag New York, Inc.

About this chapter

Cite this chapter

Chang, C. et al. (1996). A Weak Substance P Antagonist Inhibits L-692,585-Stimulated GH Release in Swine. In: Bercu, B.B., Walker, R.F. (eds) Growth Hormone Secretagogues. Serono Symposia USA Norwell, Massachusetts. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2396-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-2396-2_8

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7526-8

  • Online ISBN: 978-1-4612-2396-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics