PMID- 17143304
OWN - NLM
STAT- MEDLINE
DCOM- 20070405
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 150
IP  - 1
DP  - 2007 Jan
TI  - Neuropeptide Y modulates effects of bradykinin and prostaglandin E2 on trigeminal 
      nociceptors via activation of the Y1 and Y2 receptors.
PG  - 72-9
AB  - BACKGROUND AND PURPOSE: Although previous studies have demonstrated that 
      neuropeptide Y (NPY) modulates nociceptors, the relative contributions of the Y1 
      and Y2 receptors are unknown. Therefore, we evaluated the effect of Y1 and Y2 
      receptor activation on nociceptors stimulated by bradykinin (BK) and 
      prostaglandin E2 (PGE2). EXPERIMENTAL APPROACH: Combined immunohistochemistry 
      (IHC) with in situ hybridization (ISH) demonstrated that Y1- and Y2-receptors are 
      collocated with bradykinin (2) (B2)-receptors in rat trigeminal ganglia (TG). The 
      relative functions of the Y1 and Y2 receptors in modulating BK/PGE2-evoked CGRP 
      release and increased intracellular calcium levels in cultured TG neurons were 
      evaluated. KEY RESULTS: The Y1 and Y2 receptors are co-expressed with B2 in TG 
      neurons, suggesting the potential for direct NPY modulation of BK responses. 
      Pretreatment with the Y1 agonist [Leu31,Pro34]-NPY, inhibited BK/PGE2-evoked CGRP 
      release. Conversely, pretreatment with PYY(3-36), a Y2 agonist, increased BK/PGE2 
      evoked CGRP release. Treatment with NPY evoked an overall inhibitory effect, 
      although of lesser magnitude. Similarly, [Leu31,Pro34]-NPY inhibited 
      BK/PGE2-evoked increases in intracellular calcium levels whereas PYY(3-36) 
      increased responses. NPY inhibition of BK/PGE2-evoked release of CGRP was 
      reversed by the Y1 receptor antagonist, BIBO3304, and higher concentrations of 
      BIBO3304 significantly facilitated CGRP release. The Y2 receptor antagonist, 
      BIIE0246, enhanced the inhibitory NPY effects. CONCLUSIONS AND IMPLICATIONS: 
      These results demonstrate that NPY modulation of peptidergic neurons is due to 
      net activation of inhibitory Y1 and excitatory Y2 receptor systems. The relative 
      expression or activity of these opposing receptor systems may mediate dynamic 
      responses to injury and pain.
FAU - Gibbs, J L
AU  - Gibbs JL
AD  - Department of Pharmacology, The University of Texas Health Science Center at San 
      Antonio, TX 78229-3900, USA.
FAU - Diogenes, A
AU  - Diogenes A
FAU - Hargreaves, K M
AU  - Hargreaves KM
LA  - eng
GR  - F30 DE014326/DE/NIDCR NIH HHS/United States
GR  - R01 NS045186/NS/NINDS NIH HHS/United States
GR  - F30DE14326/DE/NIDCR NIH HHS/United States
GR  - R01 NS45186/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061204
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Neuropeptide Y)
RN  - 0 (Npy1r protein, rat)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 0 (Receptors, Neuropeptide Y)
RN  - 0 (neuropeptide Y2 receptor)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Bradykinin/*pharmacology
MH  - Dinoprostone/*pharmacology
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Male
MH  - Neuropeptide Y/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, G-Protein-Coupled/*drug effects
MH  - Receptors, Neuropeptide/*drug effects
MH  - Receptors, Neuropeptide Y/*drug effects
MH  - Trigeminal Nerve/*drug effects
PMC - PMC2013847
EDAT- 2006/12/05 09:00
MHDA- 2007/04/06 09:00
PMCR- 2008/01/01
CRDT- 2006/12/05 09:00
PHST- 2006/12/05 09:00 [pubmed]
PHST- 2007/04/06 09:00 [medline]
PHST- 2006/12/05 09:00 [entrez]
PHST- 2008/01/01 00:00 [pmc-release]
AID - 0706967 [pii]
AID - 10.1038/sj.bjp.0706967 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2007 Jan;150(1):72-9. doi: 10.1038/sj.bjp.0706967. Epub 2006 Dec 
      4.