ALPHA-1B, BUT NOT ALPHA-1A, ADRENOCEPTOR ACTIVATES CALCIUM INFLUX THROUGH THE STIMULATION OF A TYROSINE KINASE PHOSPHOTYROSINE PHOSPHATASE PATHWAY, FOLLOWING NORADRENALINE-INDUCED EMPTYING OF IP3 SENSITIVE CALCIUM STORES, IN PC CL3 RAT-THYROID CELL-LINE/

In PC Cl3 rat thyroid cell line noradrenaline-induced Ca2+ response, m ainly due to the activation of alpha 1B receptors, is characterized by a rapid peak phase, due to the Ca2+ mobilization from inositol trisph osphate-sensitive internal stores, followed by a sustained plateau, re presenting the capacitative calcium entry. The plateau phase elicited by noradrenaline returns to the basal value within 100 sec from the re moval of agonist. The tyrosine kinases inhibitor genistein completely abolishes the plateau upon noradrenaline withdrawl. On the contrary, t he tyrosine phosphatases blocker, vanadate, potentiates the plateau ph ase of calcium response to noradrenaline and prevents the gradual decr ease of [Ca2+](i) after removal of noradrenaline. The noradrenaline-in duced Ca2+ influx, due to the activation of alpha 1A receptor-operated Ca2+ entry is not affected by vanadate. The treatment with noradrenal ine induced the tyrosine phosphorylation of specific substrates in lys ates derived from PC Cl3 cells, an effect inhibited by genistein pretr eatment. These results show that a balance between tyrosine phosphoryl ation and dephosphorylation is required for the regulation of capacita tive calcium entry following noradrenaline stimulation of alpha 1B rec eptor, whilst the influx of Ca2+ directly operated by alpha 1A recepto r activation seems to be independent of the tyrosine phosphorylating p athway. (C) 1995 Academic Press, Inc.