Alpha 1 B, but not alpha 1A, adrenoreceptor 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, mainly due to the activation of alpha 1B receptors, is characterized by a rapid peak phase, due to the Ca2+ mobilization from inositol trisphosphate-sensitive internal stores, followed by a sustained plateau, representing the capacitative calcium entry. The plateau phase elicited by noradrenaline returns to the basal value within 100 sec from the removal of agonist. The tyrosine kinases inhibitor genistein completely abolishes the plateau upon noradrenaline withdrawal. On the contrary, the tyrosine phosphatases blocker, vanadate, potentiates the plateau phase of calcium response to noradrenaline and prevents the gradual decrease of [Ca2+]i after removal of noradrenaline. The noradrenaline-induced Ca2+ influx, due to the activation of alpha 1A receptor-operated Ca2+ entry is not affected by vanadate. The treatment with noradrenaline induced the tyrosine phosphorylation of specific substrates in lysates derived from PC Cl3 cells, an effect inhibited by genistein pretreatment. These results show that a balance between tyrosine phosphorylation and dephosphorylation is required for the regulation of capacitative calcium entry following noradrenaline stimulation of alpha 1B receptor, whilst the influx of Ca2+ directly operated by alpha 1A receptor activation seems to be independent of the tyrosine phosphorylating pathway.
Meucci
O
O
Dipartimento di Neuroscienze e della Comunicazione Interumana, Università degli Studi di Napoli Federico II Facoltà di Medicina e Chirurgia, Italy.
Scorziello
A
A
Avallone
A
A
Florio
T
T
D'Alto
V
V
Fattore
M
M
Schettini
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000502:physiology*; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D010750:Phosphoproteins; D011942:Receptors, Adrenergic, alpha; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D002118:Calcium; D009638:Norepinephrine