VASOACTIVE-INTESTINAL-PEPTIDE INCREASES INTRACELLULAR CALCIUM IN ASTROGLIA - SYNERGISM WITH ALPHA-ADRENERGIC RECEPTORS

In type I astrocytes from rat cerebral cortex, vasoactive intestinal p eptide (VIP) at concentrations below 1 nM evoked an increase in intrac ellular calcium ion concentration. This response, however, was observe d in only 18% of the astrocytes examined. alpha-Adrenergic stimulation with phenylephrine or norepinephrine also resulted in an intracellula r calcium response in these cells and the threshold sensitivity of ast rocytes to phenylephrine was vastly different from cell to cell. Treat ment of these astrocytes with VIP (0.1 nM) together with phenylephrine at subthreshold concentrations produced large increases in intracellu lar Ca2+ concentration ([Ca2+](i)) and oscillations. The continued occ upation of the alpha-adrenergic receptor was required for sustained sy nergism. Both alpha-receptor stimulation and stimulation with the mixt ure of agonists induced the cellular calcium response by triggering re lease of calcium from cellular stores, since the response persisted in the absence of extracellular calcium. Furthermore, thapsigargin pretr eatment, which depletes intracellular stores, abolished the agonist-in duced [Ca2+](i) response. VIP (0.1 nM) and phenylephrine were found to increase cellular levels of inositol phosphates; however, there was n o apparent additivity in this response when the agonists were added to gether. These observations suggest a calcium-mediated second messenger system for the high-affinity VIP receptor in astrocytes and that alph a-adrenergic receptors act synergistically with the VIP receptor to au gment an intracellular calcium signal. The synergism between diverse r eceptor types may constitute an important mode of cellular signaling i n astroglia.