EVIDENCE THAT A NOVEL SOMATOSTATIN RECEPTOR COUPLES TO AN INWARD RECTIFIER POTASSIUM CURRENT IN ATT-20 CELLS

The recent cloning of five somatostatin receptors has made it possible to begin screening for selective ligands in order to begin characteri zation of these receptor subtypes expressed endogenously. We have rece ntly reported the characterization of ligands selective for SSTR2 and SSTR5 [Raynor K. et al. (1993) Molec. Pharmac. 43, 838-844; 44, 385-39 2]. Both of these somatostatin receptor subtypes are endogenously expr essed in the mouse pituitary cell line At T-20 [O'Carroll A.-M. et al. (1992) Molec. Pharmac. 42, 939-946; Patel Y. C. et al. (1994) J. biol . Chem. 269, 1506-1509; Tallent M. et al. (1996) Neuroscience 71, 1073 -1081]. Using these selective ligands, as well as other somatostatin a nalogs, we have characterized the somatostatin receptor which couples to the inward rectifier K+ current in At T-20 cells. This receptor is sensitive to hexapeptide analogs of somatostatin, but insensitive to o ctapeptide analogs. This pharmacological profile is distinct from any of the cloned somatostatin receptors and therefore may represent a nov el receptor. Somatostatin has been shown to potentiate an inward recti fying K+ channel in many different types of neuronal and non-neuronal cells. The activation of this current is thought to be an important me chanism by which somatostatin inhibits neuronal firing and decreases n eurotransmitter and hormone release [Mihara S. et al. (1987) J. Physio l. 390, 335-355]. Therefore, the novel somatostatin receptor coupling to the inward rectifier in At T-20 cells may be important in somatosta tin's role in regulating neurotransmission and hormone release. Copyri ght (C) 1996 IBRO. Published by Elsevier Science Ltd.