Reciprocal modulation of phospholipase Cβ isoforms: Adaptation to chronic morphine

• DOI: 10.1073/pnas.2335885100
• Publication Date: 2003-11-16T20:42:47Z
• Authors: Sumita Chakrabarti; Nai-Jiang Liu; Alan R. Gintzler
• Keywords: 0303 health sciences; Time Factors; Morphine; Naloxone; Acclimatization; Blotting, Western; Guinea Pigs; Phospholipase C beta; Drug Tolerance; Cyclic AMP-Dependent Protein Kinases; Precipitin Tests; Up-Regulation; Analgesics, Opioid; Isoenzymes; 03 medical and health sciences; Type C Phospholipases; Animals; Protein Isoforms; Phosphorylation; Protein Kinase C; Signal Transduction

Phosphoinositide turnover and calcium mobilization are fundamental determinants of acute chronic opioid effects. Phosphoinositide-specific phospholipase C (PLC) key signaling enzymes that play a pivotal role in mediating modulation inositol trisphosphate production cytosolic distribution, substrates for many Notably, phosphorylation the β isoforms PLC, by kinases up-regulated after morphine, is potent modality their regulation. Direct assessment PLCβ1 PLCβ3 guinea pig longitudinal muscle myenteric plexus tissue revealed substantial alterations induction tolerance. direction this isoform-specific. Phosphorylation significantly reduced, whereas substantially augmented, changes not accompanied altered content or protein. In contrast to morphine treatment naïve attenuates phosphorylation, an effect also manifested endogenous opioids reflected ability naloxone augment phosphorylation. This indicates PLCβ dynamically regulated. activities negatively modulated Thus, concomitant reciprocal would alter relative contribution these PLC/Ca 2+ signaling, significant shift light differential regulatory characteristics. Reciprocal (activity) two within same subclass enzyme, proteins have high degree structural similarity subserve biological function, represents adaptation has heretofore been recognized.