Premium
Second messenger‐dependent protein kinases and protein synthesis regulate endogenous secretin receptor responsiveness
Author(s) -
Ghadessy Roxana S,
Kelly Eamonn
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704655
Subject(s) - forskolin , protein kinase c , medicine , endocrinology , secretin , second messenger system , adenosine , receptor , protein kinase a , agonist , biology , chemistry , signal transduction , stimulation , microbiology and biotechnology , kinase , secretion
The present study investigated the role of second messenger‐dependent protein kinase A (PKA) and C (PKC) in the regulation of endogenous secretin receptor responsiveness in NG108‐15 mouse neuroblastoma×rat glioma hybrid cells. In whole cell cyclic AMP accumulation studies, activation of PKC either by phorbol 12‐myristate 13‐acetate (PMA) or by purinoceptor stimulation using uridine 5′‐triphosphate (UTP) decreased secretin receptor responsiveness. PKC activation also inhibited forskolin‐stimulated cyclic AMP accumulation but did not affect cyclic AMP responses mediated by the prostanoid‐IP receptor agonist iloprost, or the A 2 adenosine receptor agonist 5′‐( N ‐ethylcarboxamido) adenosine (NECA). In additivity experiments, saturating concentrations of secretin and iloprost were found to be additive in terms of cyclic AMP accumulation, whereas saturating concentrations of NECA and iloprost together were not. This suggests compartmentalization of G s ‐coupling components in NG108‐15 cells and possible heterologous regulation of secretin receptor responsiveness at the level of adenylyl cyclase activation. Cells exposed to the PKA inhibitor H‐89, exhibited a time‐dependent increase in secretin receptor responsiveness compared to control cells. This effect was selective since cyclic AMP responses to forskolin, iloprost and NECA were not affected by H‐89 treatment. Furthermore, treatment with the protein synthesis inhibitor cycloheximide produced a time‐dependent increase in secretin receptor responsiveness. Together these results indicate that endogenous secretin receptor responsiveness is regulated by PKC, PKA and protein neosynthesis in NG108‐15 cells.British Journal of Pharmacology (2002) 135 , 2020–2028; doi: 10.1038/sj.bjp.0704655