PMID- 9927621
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 55
IP  - 2
DP  - 1999 Feb
TI  - No role for Ca++ or protein kinase C in alpha-1A adrenergic receptor activation 
      of mitogen-activated protein kinase pathways in transfected PC12 cells.
PG  - 296-303
AB  - We studied the role of Ca++ and protein kinase C (PKC) in alpha-1A adrenergic 
      receptor (AR)-mediated activation of mitogen-activated protein kinase pathways in 
      PC12 cells. In PC12 cells stably transfected with the human alpha-1A AR, 
      norepinephrine (NE) strongly activated both extracellular signal regulated 
      kinases (ERKs) and c-jun-NH2-terminal kinases (JNK). Ten nanomolar thapsigargin 
      (TG) increased cytoplasmic Ca++ at least as much as NE but did not activate ERKs 
      or JNK. Higher concentrations of TG caused a small activation of ERKs but not 
      JNK. Emptying [Ca++]i stores by pretreatment with TG prevented the NE-stimulated 
      increase in [Ca++]i but not ERK or JNK activation. The Ca++ chelator 
      bis(2-aminophenoxy)ethane-N-N-N'-N'-tetraacetate (BAPTA) dose dependently 
      abolished NE-stimulated Ca++ responses but not ERK or JNK activation. NE 
      increased tyrosine phosphorylation of Pyk2, and this response was neither blocked 
      by BAPTA nor mimicked by TG. The phorbol ester tumor promoting agent (TPA) caused 
      a dose-dependent activation of ERKs that was potentiated by 10 nM TG. TPA caused 
      only a small activation of JNK relative to that caused by NE, which was not 
      affected by TG. The potent PKC inhibitor bisindolylmaleimide I dose dependently 
      inhibited ERK and JNK activation by TPA, but not NE. ATP and UTP activated 
      similar mitogen-activated protein kinase responses through endogenous P2Y2 
      receptors, and these responses were not blocked by BAPTA or bisindolylmaleimide 
      I, suggesting that these results may be generalizable to other Gq/11-coupled 
      receptors. The results suggest that Ca++ release and PKC activation are neither 
      necessary nor sufficient for alpha-1A AR-mediated activation of mitogenic 
      responses in PC12 cells.
FAU - Berts, A
AU  - Berts A
AD  - Department of Pharmacology, Emory University School of Medicine, Atlanta, 
      Georgia, USA. kmlab@pharm.emory.edu
FAU - Zhong, H
AU  - Zhong H
FAU - Minneman, K P
AU  - Minneman KP
LA  - eng
GR  - NS 32706/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (ADRA1A protein, human)
RN  - 0 (Adra1a protein, rat)
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Carcinogens)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Ionophores)
RN  - 0 (Maleimides)
RN  - 0 (P2RY2 protein, human)
RN  - 0 (P2ry2 protein, rat)
RN  - 0 (Receptors, Adrenergic, alpha-1)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Ptk2b protein, rat)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - L79H6N0V6C (bisindolylmaleimide I)
RN  - SY7Q814VUP (Calcium)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic alpha-Agonists/pharmacology
MH  - Animals
MH  - Calcimycin/pharmacology
MH  - Calcium/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/*metabolism
MH  - Carcinogens/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Focal Adhesion Kinase 2
MH  - Humans
MH  - Indoles/pharmacology
MH  - Ionophores/pharmacology
MH  - Maleimides/pharmacology
MH  - Norepinephrine/pharmacology
MH  - PC12 Cells
MH  - Protein Kinase C/drug effects/metabolism/*physiology
MH  - Protein-Tyrosine Kinases/drug effects/metabolism
MH  - Rats
MH  - Receptors, Adrenergic, alpha-1/genetics/*metabolism
MH  - Receptors, Purinergic P2/drug effects/metabolism
MH  - Receptors, Purinergic P2Y2
MH  - Thapsigargin/pharmacology
MH  - Transfection
EDAT- 1999/02/03 00:00
MHDA- 1999/02/03 00:01
CRDT- 1999/02/03 00:00
PHST- 1999/02/03 00:00 [pubmed]
PHST- 1999/02/03 00:01 [medline]
PHST- 1999/02/03 00:00 [entrez]
AID - 10.1124/mol.55.2.296 [doi]
PST - ppublish
SO  - Mol Pharmacol. 1999 Feb;55(2):296-303. doi: 10.1124/mol.55.2.296.