title: Ligand Binding and Functional Properties of the Rat Somatostatin Receptor SSTR4 Stably Expressed in Chinese Hamster Ovary Cells.
abstract: Somatostatin (SS14) is an important regulator of endocrine and brain function exerting its action after binding to high-affinity membrane receptor subtypes. Its diverse physiological activities include inhibition of hormone secretion from pituitary, pancreas, and gut. In the CNS, SS14 acting as a neurotransmitter/neuromodulator exerts inhibitory effects on neural function. Recently, three SS14 receptor genes, SSTR1, SSTR2, and SSTR3, have been cloned and characterized. We have cloned and characterized a novel fourth member of this gene family from a rat genomic library, SSTR4, which is expressed predominantly in neural tissue. When stably expressed in CHO-K1 cells, SSTR4 binds SS14 and SS28 with high affinity; however, the SS14 analogs SMS 201-995 and MK 678 failed to displace specific binding. High-affinity agonist binding was diminished by prior exposure to both GTPgammaS and pertussis toxin (PTX) but was not effected following agonist pretreatment, indicating that SSTR4 is coupled to a PTX-sensitive G-protein but does not desensitize. SSTR4 expressed in CHO cells is coupled by a PTX-sensitive G-protein to inhibition of adenylyl cyclase since treatment of transfected cells with SS14 resulted in the inhibition of forskolin-stimulated cAMP accumulation, an effect that was abolished by PTX treatment. The cloning of four SS14 receptor subtypes provide molecular probes for structure-function studies and for identifying those particular subtypes responsible for mediating the diverse physiological action of SS14.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine and Department of Physiology and Biophysics (MB), State University of New York at Stony Brook, Stony Brook, New York 11794.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: Berelowitz
authors.forename: J F
authors.initials: JF
authors.lastname: Bruno