Physics And Chemistry Basis Of Biotechnology - De Cuyper - tiera.ru

FUNCTIONAL STRUCTURE OF THE SECRETIN RECEPTOR
Abstract
P. ROBBERECHT 1 , M. WAELBROECK 1 , AND
N. MOGUILEVSKY 2 .
1 Department of Biochemistry and Nutrition, Faculty of Medicine
2 Department of Applied Genetics, IBMM, Faculty of Sciences,
Université Libre de Bruxelles, Belgium.
Secretin is a 27 amino acid peptide secreted by specialised endocrine cells of the gut
that regulates the pancreatic exocrine - and the liver bile secretions. Its role as a
neuropeptide is likely but not yet proven. Secretin acts through interaction with a
membrane receptor coupled to the G as protein and thus stimulates cyclic AMP
production. It belongs to a new subgroup of receptors named the GPCRB that includes
- among others - the VIP, the PACAP, the Glucagon, the Glucagon like peptide 1, the
Calcitonin and the Parathormone receptors. The expression in CHO cells of the wild
type and of mutated receptors permits the identification of domains involved in ligand
recognition, in signal transduction, in desensitisation and in receptor intemalisation.
1. Introduction
Bayliss and Starling, in 1902, discovered that acid extracts of the mucosa of the upper
intestine contained a substance that, if injected into the blood stream caused the
pancreas to secrete. They named the substance Secretin. They suggested a new term
"hormone" to describe such chemical messengers between different organs. The
purification of Secretin was undertaken at the Karolinska Institute by Jorpes and Mutt
and the amino acid sequence definitively established in 1970. At the same time,
Bodansky synthesised the 27 amino acid peptide that had a biological activity
indistinguishable from that of the natural hormone [ 1]. Secretin had marked similarities
to Glucagon that was sequenced before. Later on, sequences similarities were found
with newly discovered peptides VIP, GIP, GRF, PACAP, PHI, GLP-1, and GLP-2. The
existence of a large family of biologically active peptides with sequence similarities but
different properties was established [2].
Using isolated pancreatic acini or acinar cells, it was shown that Secretin acted
through interaction with a specific membrane receptor coupled to adenylate cyclase [3].
167
M. De Cuyper and J.W.M. Bulte (eds.), Physics and Chemistry Basis of Biotechnology, 161-176.
© 2001 Kluwer Academic Publishers. Printed in the Netherlands.