ALTERATIONS IN CA2-CELLS OF RESERPINE-TREATED RATS( STORAGE AND MOBILIZATION IN SUBMANDIBULAR ACINAR)

The present study investigated the effects of the catecholamine-deplet ing drug reserpine on cellular Ca2+ storage and mobilization in rat su bmandibular acinar cells. Adult rats received seven daily injections o f reserpine (0.5 mg/kg) and inositol 1,4,5-trisphosphate (IP3) formati on and Ca2+ mobilization were measured in isolated submandibular acina r cells. Ultrastructural analysis demonstrated a significant reduction in rough endoplasmic reticulum (ER) and a dramatic accumulation of se cretory granules in the cells of treated animals. Reserpine reduced ac etylcholine (ACh)-stimulated IP3 formation by 46% and the initial incr ease in cytosolic Ca2+ concentration ([Ca2+](i)) in response to ACh or thapsigargin was reduced by 21 and 56%, respectively. While norepinep hrine (NE) did not induce significant IP3 formation, the [Ca2+](i) res ponse to NE was increased 360% by reserpine treatment. Reserpine treat ment also enhanced the sustained [Ca2+](i) increase following these st imuli. After stimulation with ACh or NE, exposure to ionomycin caused a further elevation in [Ca2+](i) which was significantly larger in the cells of treated animals. After exposure to agonist + ionomycin, addi tion of monensin induced a third increase in [Ca2+](i) which was signi ficantly larger in cells of reserpine-treated animals. While capacitat ive Ca2+ entry was not altered, NE activated Ca2+ influx was abolished after reserpine treatment. Reserpine treatment therefore alters IP3-s ensitive and insensitive Ca2+ stores, non-capacitative Ca2+ influx and active Ca2+ transport in submandibular acinar cells of rats. (C) 1998 Elsevier Science Inc. All rights reserved.