PMID- 10748146
OWN - NLM
STAT- MEDLINE
DCOM- 20000711
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 22
DP  - 2000 Jun 2
TI  - Pituitary adenylyl cyclase-activating peptide activates multiple intracellular 
      signaling pathways to regulate ion channels in PC12 cells.
PG  - 16626-31
AB  - Pituitary adenylyl cyclase-activating peptide (PACAP) stimulates calcium 
      transients and catecholamine secretion in adrenal chromaffin and PC12 cells. The 
      PACAP type 1 receptor in these cells couples to both adenylyl cyclase and 
      phospolipase C pathways, but although phospolipase C has been implicated in the 
      response to PACAP, the role of adenylyl cyclase is unclear. In this study, we 
      show that PACAP38 stimulates Ca(2+) influx in PC12 cells by activating a cation 
      current that depends upon the dual activation of both the PLC and adenylyl 
      cyclase signaling pathways but does not involve protein kinase C. In activating 
      the current, PACAP38 has to overcome an inhibitory effect of Ras. Thus, in cells 
      expressing a dominant negative form of Ras (PC12asn17-W7), PACAP38 induced 
      larger, more rapidly activating currents. This effect of Ras could be overidden 
      by intracellular guanosine-5'-O-3-(thio)triphosphate (GTPgammaS), suggesting that 
      it was mediated by inhibition of downstream G proteins. Ras may also inhibit the 
      current through a G protein-independent mechanism, because cAMP analogues 
      activated the current in PC12asn17-W7 cells, provided GTPgammaS was present, but 
      not in PC12 cells expressing wild type Ras. We conclude that coupling of PACAP to 
      both adenylyl cyclase and phospholipase C is required to activate Ca(2+) influx 
      in PC12 cells and that tonic inhibition by Ras delays and limits the response.
FAU - Osipenko, O N
AU  - Osipenko ON
AD  - Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G4 
      ONR, United Kingdom.
FAU - Barrie, A P
AU  - Barrie AP
FAU - Allen, J M
AU  - Allen JM
FAU - Gurney, A M
AU  - Gurney AM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adcyap1 protein, rat)
RN  - 0 (Calcium Channels)
RN  - 0 (Neuropeptides)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.6.5.2 (Oncogene Protein p21(ras))
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclases/metabolism
MH  - Animals
MH  - Calcium Channels/metabolism/*physiology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/physiology
MH  - Membrane Potentials/physiology
MH  - Neuropeptides/metabolism/*physiology
MH  - Oncogene Protein p21(ras)/physiology
MH  - PC12 Cells
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide
MH  - Rats
MH  - Signal Transduction/*physiology
MH  - Type C Phospholipases/metabolism
EDAT- 2000/04/05 09:00
MHDA- 2000/07/15 11:00
CRDT- 2000/04/05 09:00
PHST- 2000/04/05 09:00 [pubmed]
PHST- 2000/07/15 11:00 [medline]
PHST- 2000/04/05 09:00 [entrez]
AID - S0021-9258(19)80252-1 [pii]
AID - 10.1074/jbc.M909636199 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jun 2;275(22):16626-31. doi: 10.1074/jbc.M909636199.