Characterisation of proghrelin peptides in mammalian tissue and plasma

Abstract

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).