PMID- 24303997
OWN - NLM
STAT- MEDLINE
DCOM- 20141105
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 171
IP  - 6
DP  - 2014 Mar
TI  - PACAP receptor pharmacology and agonist bias: analysis in primary neurons and 
      glia from the trigeminal ganglia and transfected cells.
PG  - 1521-33
LID - 10.1111/bph.12541 [doi]
AB  - BACKGROUND AND PURPOSE: A major challenge in the development of new medicines 
      targeting GPCRs is the ability to quantify drug action in physiologically 
      relevant models. Primary cell models that closely resemble the clinically 
      relevant in vivo site of drug action are important translational tools in drug 
      development. However, pharmacological studies in these models are generally very 
      limited due to the methodology used. EXPERIMENTAL APPROACH: We used a 
      neuropeptide system to demonstrate the applicability of using highly sensitive 
      signalling assays in primary cells. We quantified the action of pituitary 
      adenylate cyclase-activating peptide (PACAP)-38, PACAP-27 and vasoactive 
      intestinal polypeptide in primary cultures of neurons and glia derived from rat 
      trigeminal ganglia (TG), comparing our observations to transfected cells. KEY 
      RESULTS: PACAP-responsive receptors in rat trigeminal neurons, glia and 
      transfected PAC1n receptors were pharmacologically distinct. PACAP-38, but not 
      PACAP-27, activated ERK in glia, while both forms stimulated cellular cAMP 
      production. PACAP(6-38) also displayed cell-type-dependent, agonist-specific, 
      antagonism. CONCLUSIONS AND IMPLICATIONS: The complexity of PACAP pharmacology in 
      the TG may help to direct, more effectively, the development of disease 
      treatments targeting the PACAP receptor. We suggest that these methodologies are 
      broadly applicable to other primary cell types of human or animal origin, and 
      that our approach may allow more thorough characterization of ligand properties 
      in physiologically relevant cell types.
CI  - (c) 2013 The British Pharmacological Society.
FAU - Walker, C S
AU  - Walker CS
AD  - School of Biological Sciences, University of Auckland, Auckland, New Zealand; 
      Centre for Brain Research, University of Auckland, Auckland, New Zealand.
FAU - Sundrum, T
AU  - Sundrum T
FAU - Hay, D L
AU  - Hay DL
LA  - eng
SI  - GENBANK/AY366498
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide)
SB  - IM
CIN - Br J Pharmacol. 2015 Oct;172(19):4782-4. PMID: 24826981
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Molecular Sequence Data
MH  - Neuroglia/cytology/*drug effects
MH  - Neurons/cytology/*drug effects
MH  - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/agonists/*drug 
      effects
MH  - *Transfection
PMC - PMC3954490
OTO - NOTNLM
OT  - G-protein coupled receptor
OT  - PAC1
OT  - PACAP
OT  - VIP
OT  - bias signalling
OT  - glia
OT  - intracellular signalling
OT  - neuron
OT  - primary culture
OT  - trigeminal ganglia
EDAT- 2013/12/07 06:00
MHDA- 2014/11/06 06:00
PMCR- 2015/03/01
CRDT- 2013/12/06 06:00
PHST- 2013/09/09 00:00 [received]
PHST- 2013/11/25 00:00 [revised]
PHST- 2013/11/29 00:00 [accepted]
PHST- 2013/12/06 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/11/06 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - 10.1111/bph.12541 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2014 Mar;171(6):1521-33. doi: 10.1111/bph.12541.