Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat.
We have recently reported oral and parenteral bioactivity for a new GH-releasing peptide, hexarelin. In the present study, we have examined the neuroendocrine mechanism by which hexarelin and GHRP-6, two GH-releasing peptides, mediate their actions. Although previous studies have looked at the role of growth hormone-releasing hormone (GHRH) and somatostatin in regulating the action of GHRP-6 in culture and in stressed animals, our study looked at the role of both somatostatin and GHRH in regulating the action of hexarelin as well as GHRP-6 in conscious and freely-moving, nonstressed rats. Adult male rats, prepared with indwelling jugular catheters, were pretreated i.v. with either control antiserum (CTLas), growth hormone-releasing hormone antiserum (GHRHas), somatostatin antiserum (SSas), or both GHRHas and SSas. Animals were then treated i.v. with 25 micrograms/kg of either hexarelin or GHRP-6 4 h after i.v. antisera pretreatment. Blood samples were collected every 20 min for the 3 h prior to peptide treatment and at 5, 10, 15, 20, 40 and 60 min following hexarelin or GHRP-6 injection. The peak plasma GH responses in rats pretreated with CTLas were 552 +/- 125 ng/ml following hexarelin administration and 386 +/- 132 ng/ml following GHRP-6 administration. Rats pretreated with SSas exhibited peak GH responses following hexarelin or GHRP-6 of 702 +/- 115 and 312 +/- 42 ng/ml, respectively. These plasma GH responses were similar to those observed in the CTLas-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Conley
L K
LK
Department of Biological Sciences, University of Wisconsin-Milwaukee 53201.
Teik
J A
JA
Deghenghi
R
R
Imbimbo
B P
BP
Giustina
A
A
Locatelli
V
V
Wehrenberg
W B
WB
D000595:Amino Acid Sequence; D000818:Animals; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology*; D007116:Immunization, Passive; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000276:immunology / Q000502:physiology*
D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone