Alterations in Ca2+ storage and mobilization in submandibular acinar cells of reserpine-treated rats

The present study investigated the effects of the catecholamine-depleting drug reserpine on cellular Ca2+ storage and mobilization in rat submandibular acinar cells. Adult rats received seven daily injections of reserpine (0.5 mg/kg) and inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization were measured in isolated submandibular acinar cells. Ultrastructural analysis demonstrated a significant reduction in rough endoplasmic reticulum (ER) and a dramatic accumulation of secretory granules in the cells of treated animals. Reserpine reduced acetylcholine (ACh)-stimulated IP3 formation by 46% and the initial increase in cytosolic Ca2+ concentration ([Ca2+]i) in response to ACh or thapsigargin was reduced by 21 and 56%, respectively. While norepinephrine (NE) did not induce significant IP3 formation, the [Ca2+]i response to NE was increased 360% by reserpine treatment. Reserpine treatment also enhanced the sustained [Ca2+]i increase following these stimuli. 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, addition of monensin induced a third increase in [Ca2+]i which was significantly larger in cells of reserpine-treated animals. While capacitative Ca2+ entry was not altered, NE-activated Ca2+ influx was abolished after reserpine treatment. Reserpine treatment therefore alters IP3-sensitive and insensitive Ca2+ stores, non-capacitative Ca2+ influx and active Ca2+ transport in submandibular acinar cells of rats.