title: Characterization of human and rat glucagon-like peptide-1 receptors in the neurointermediate lobe: lack of coupling to either stimulation or inhibition of adenylyl cyclase.
abstract: Glucagon-like peptide-1 (GLP-1) has been shown to bind to the posterior pituitary in the rat. We examined GLP-1 binding sites in human postmortem and rat pituitaries. Dense [125I]GLP-1 binding was seen in both human and rat posterior pituitary. In rat neurointermediate lobe membranes the binding site showed a Kd of 0.2 +/- 0.01 nM and a binding capacity of 600 +/- 33 fmol/mg protein (n = 3). In human pituitary membranes the binding site showed a Kd of 0.82 +/-0.05 nM and a binding capacity of 680 +/- 93 fmol/mg protein (n = 3). Chemical cross-linking showed a relative mol wt for the receptor-ligand complex of 73,100 +/- 1,400 (n = 3) in man and 59,300 +/- 900 (n = 3) in rat. GLP-1 (1 microM) failed to increase cAMP levels measured in rat neurointermediate lobes, whereas pituitary adenylate cyclase-activating polypeptide (100 nM) increased cAMP from a basal level of 14 +/-1 to 80 +/- 4 pmol/neurointermediate lobe 15 min (n = 5; P < 0.01). GLP-1 (up to 1 microM) did not affect the pituitary adenylate cyclase-activating polypeptide-stimulated cAMP levels. GLP-1 (up to 1 microM) also did not stimulate release of vasopressin or oxytocin from isolated rat neurointermediate lobes. The posterior pituitary shows the highest density of GLP-1-binding sites yet seen, but their function and signal transduction mechanism remain unknown.
authors.affiliation: Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Satoh
authors.forename: S A
authors.initials: SA
authors.lastname: Beak
authors.forename: C J
authors.initials: CJ
authors.lastname: Small
authors.forename: M
authors.initials: M
authors.lastname: Falzon
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: D M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001345:Autoradiography; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008297:Male; D008566:Membranes / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D001127:Arginine Vasopressin; D010121:Oxytocin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases