NOREPINEPHRINE INDUCES CA2+ RELEASE FROM INTRACELLULAR STORES IN RAT PINEALOCYTES

In rat pinealocytes, an increase in intracellular Ca2+ concentration ( [Ca2+](i)) due to Ca2+ influx in response to norepinephrine (NE) is a well recognized event involved in regulating several metabolic functio ns. Since NE also stimulates the metabolism of phosphatidyl inositols in rat pineal gland, it is conceivable that Ca2+ release from intracel lular stores also contributes to the NE-induced increase in [Ca2+](i). In this communication, we report that in rat pinealocytes loaded with fura-2, a Ca2+ indicator, NE induced a transient increase in [Ca2+](i ) that preceded the known Ca2+ influx. This novel [Ca2+](i) response t o NE was detected in pinealocytes bathed with Ca2+-free saline and pre vented by TMB-8, a blocker of Ca2+ release from intracellular stores, supporting the notion that the transient NE-induced Ca2+ response was due to Ca2+ release from intracellular stores. In addition, after an e xtended exposure to NE a new addition of this neurotransmitter did not elicit the phasic Ca2+ response, and application of increasing amount s of NE induced a Ca2+ response that was progressively smaller, sugges ting desensitization. Thus, NE is proposed to increase [Ca2+](i) in ra t pinealocytes by two mechanisms: (1) phasic release from intracellula r stores and (2) tonic influx through a mechanism activated by larger applications of NE than required to evoke the phasic release.