Internalization of neuropeptide Y Y1 and Y5 and of pancreatic polypeptide Y4 receptors is inhibited by lithium in preference to sodium and potassium ions.
The receptor-linked internalization of [125I] human neuropeptide Y (NPY) in Chinese hamster ovary (CHO) cells expressing the guinea-pig Y1 receptors or in human endometrial carcinoma-1B (Hec-1B) cells expressing the human Y5 receptor, as well as the receptor-linked internalization of human pancreatic polypeptide (hPP) receptor expressed in CHO cells, is selectively inhibited by low molarities of the Li+ cation. The Na+ and K+ cations decreased the receptor-linked internalization of agonist peptides only at high molar inputs, and largely in proportion to the reduction of cell surface binding of Y ligand peptides, dependent on ion concentration and the type of Y receptor examined. With particulates isolated from disrupted cells, there was no preferential inhibition by Li+ relative to Na+ in the binding of type-specific ligand peptides to Y receptors of any type. The observed difference could be connected to the known ability of Li+ to modify active conformations of signal transducers, which may also directly or indirectly affect the internalization motors. The decrease in the rate of Y receptor internalization by Li+ also points to a possible alteration of Y receptor signaling in vivo by lithium at acute therapeutically employed dose levels.
Parker
Michael S
MS
Department of Microbiology and Molecular Cell Sciences, University of Memphis, Memphis, TN 38152, USA.
Parker
Steven L
SL
Kane
Justin K
JK
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D008024:Ligands; D008094:Lithium / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000378:metabolism / Q000493:pharmacokinetics; D010191:Pancreatic Polypeptide / Q000378:metabolism / Q000493:pharmacokinetics; D011188:Potassium / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology*
D008024:Ligands; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide; D008094:Lithium; D012964:Sodium; D011188:Potassium