Abstract
We recently reported that submandibular gland acinar cells express both the α1A‐ and α1B‐AR subtypes; however, the function of these subtypes in acinar cells is unknown. Extracellular signal‐regulated kinases (ERK 1/2) are important signaling molecules in the mitogen‐activated protein kinase family. Preliminary studies indicated the neurotransmitter norepinephrine stimulates ERK 1/2 in acinar cells; however, nothing is known about the α1‐AR subtype and its signal transduction pathway activating ERK 1/2. Thus, we used Western blot analysis to characterize the α1‐AR subtype and its signaling pathway for activating ERK 1/2 phosphorylation in submandibular gland acinar cells.
Phenylephrine (10 – 100 μM) stimulated a 4‐fold increase in phosphorylated ERK 1/2 over basal that was blocked by 100 nM prazosin but not by 20 nM 5‐methylurapidil. In addition, chloroethylclonidine completely inhibited phenylephrine‐stimulated ERK 1/2. Taken together, these results indicate that the α1B‐AR subtype, but not the α1A‐AR subtype, stimulates ERK 1/2 phosphorylation in acinar cells. U73122 (phospholipase C inhibitor, 10μM), GF109203X (protein kinase C inhibitor, 200 nM), and AG1478 (inhibitor of epidermal growth factor receptor tyrosine kinase, 100 nM) blocked activation of ERK 1/2 by phenylephrine. These data indicate phospholipase C, protein kinase C and transactivation of the epidermal growth factor receptor play a role in the signaling pathway for α1B‐adrenoceptor activation of ERK 1/2 in submandibular gland acinar cells.
(Supported by NIH RO3‐DE12530 to C.S.B.)