Characterisation of proghrelin peptides in mammalian tissue and plasma.
Ghrelin is a 28 amino acid stomach peptide, derived from proghrelin(1-94), that stimulates GH release, appetite and adipose deposition. Recently, a peptide derived from proghrelin(53-75) -- also known as obestatin -- has been reported to be a physiological antagonist of ghrelin in the rat. Using four specific RIAs, we provide the first characterisation of proghrelin(1-94) peptides in human plasma, their modulation by metabolic manipulation and their distribution in mammalian tissues. ghrelin(1-28) immunoreactivity (IR) in human plasma and rat plasma/stomach consisted of major des-octanoyl and minor octanoylated forms, as determined by HPLC/RIA. Human plasma ghrelin(1-28) IR was significantly suppressed by food intake, oral glucose and 1 mg s.c. glucagon administration. ghrelin(1-28) IR and proghrelin(29-94) IR peptide distributions in the rat indicated that the stomach and gastrointestinal tract contain the highest amounts of the peptides. Human and rat plasma and rat stomach extracts contained a major IR peak of proghrelin(29-94)-like peptide as determined by HPLC/RIA, whereas no obestatin IR was observed. Human plasma proghrelin(29-94)-like IR positively correlated with ghrelin(1-28) IR, was significantly suppressed by food intake and oral glucose and shared with ghrelin(1-28) IR a negative correlation with body mass index. We found no evidence for the existence of obestatin as a unique, endogenous peptide. Rather, our data suggest that circulating and stored peptides derived from the carboxyl terminal of proghrelin (C-ghrelin) are consistent in length with proghrelin(29-94) and respond to metabolic manipulation, at least in man, in similar fashion to ghrelin(1-28).
Bang
Angela S
AS
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, New Zealand.
Soule
Steven G
SG
Yandle
Tim G
TG
Richards
A Mark
AM
Pemberton
Chris J
CJ
D000328:Adult; D000368:Aged; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005215:Fasting; D005260:Female; D041981:Gastrointestinal Tract / Q000737:chemistry*; D054439:Ghrelin; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007328:Insulin / Q000097:blood; D007422:Intestines / Q000737:chemistry; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood; D036361:Peptide Hormones / Q000032:analysis* / Q000097:blood; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000737:chemistry
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D010446:Peptide Fragments; D036361:Peptide Hormones; D011498:Protein Precursors; C505799:obestatin, human; C505798:obestatin, rat; D005934:Glucagon; D005947:Glucose