PMID- 18694807
OWN - NLM
STAT- MEDLINE
DCOM- 20090203
LR  - 20231213
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 443
IP  - 3
DP  - 2008 Oct 10
TI  - Nociceptin/orphanin FQ causes non-quantal slowing of respiratory rhythm in 
      brainstem-spinal cord preparation from newborn rat.
PG  - 129-33
LID - 10.1016/j.neulet.2008.08.002 [doi]
AB  - Nociceptin/orphanin FQ (N/OFQ) is the endogenous agonist of the N/OFQ peptide 
      receptor, an inhibitory G protein-coupled receptor. N/OFQ acts as a 
      neuromodulator to depress respiratory rhythm in the brainstem. Although the 
      mechanisms of respiratory rhythm generation remain poorly understood, the 
      pre-inspiratory neuron (Pre-I) and the pre-Botzinger complex (preBotC) 
      inspiratory neuron (Insp) network in the rostral ventrolateral medulla (RVLM) 
      have been proposed to be essential for respiratory rhythm generation. Opioids 
      presumably cause quantal slowing via selective depression of preBotC Insps. 
      However, it is unclear whether N/OFQ depresses respiratory rhythm via the same 
      mechanism. In this study, using in vitro newborn rat en bloc preparations, we 
      examined the slowing pattern of N/OFQ (quantal or non-quantal) and the effects of 
      N/OFQ on the extracellularly recorded discharge of Pre-Is and Insps in the RVLM. 
      N/OFQ caused non-quantal slowing with a synchronous decrease in burst rates of 
      Insps and of C4 discharge whereas the intraburst spike number in Insps remained 
      unchanged. It also caused a significant decrease in burst rates and intraburst 
      spike numbers in Pre-Is, while the 1:1 coupling of Pre-Is bursts to C4 bursts was 
      preserved. When superfusate K(+) was elevated from 6.2 to 11.2mM, Pre-I activity 
      was increasingly uncoupled from C4 bursts. After the application of N/OFQ in a 
      high [K(+)] superfusate, the 1:1 coupling of Pre-Is to C4 bursts was restored. We 
      conclude that N/OFQ suppresses burst and spike generation of Pre-Is, and that 
      suppression of Pre-Is activity with synchronous coupling to the Insps network 
      contributes to N/OFQ-induced non-quantal slowing.
FAU - Takita, Koichi
AU  - Takita K
AD  - Department of Anesthesiology, Hokkaido University Graduate School of Medicine, 
      Sapporo 060-8638, Japan. ktaika@med.hokudai.ac.jp
FAU - Morimoto, Yuji
AU  - Morimoto Y
LA  - eng
PT  - Journal Article
DEP - 20080807
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Opioid Peptides)
RN  - 660YQ98I10 (Potassium Chloride)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Animals, Newborn
MH  - Brain Stem/cytology/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - In Vitro Techniques
MH  - Neural Pathways/drug effects/physiology
MH  - Neurons/drug effects/physiology
MH  - Opioid Peptides/*pharmacology/physiology
MH  - Potassium Chloride/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Respiratory Mechanics/drug effects/*physiology
MH  - Spinal Cord/cytology/*drug effects/physiology
MH  - Time Factors
MH  - Nociceptin
EDAT- 2008/08/13 09:00
MHDA- 2009/02/04 09:00
CRDT- 2008/08/13 09:00
PHST- 2008/05/11 00:00 [received]
PHST- 2008/08/01 00:00 [revised]
PHST- 2008/08/01 00:00 [accepted]
PHST- 2008/08/13 09:00 [pubmed]
PHST- 2009/02/04 09:00 [medline]
PHST- 2008/08/13 09:00 [entrez]
AID - S0304-3940(08)01088-4 [pii]
AID - 10.1016/j.neulet.2008.08.002 [doi]
PST - ppublish
SO  - Neurosci Lett. 2008 Oct 10;443(3):129-33. doi: 10.1016/j.neulet.2008.08.002. Epub 
      2008 Aug 7.