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

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 K_d 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 K_d 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 μM) 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 μM) did not affect the pituitary adenylate cyclase-activating polypeptide-stimulated cAMP levels. GLP-1 (up to 1 μM) 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.