TY - JOUR
T1 - Mu opioid receptors in rat ventral medulla
T2 - Effects of endomorphin-1 on phrenic nerve activity
AU - Lonergan, Tina
AU - Goodchild, Ann K.
AU - Christie, Macdonald J.
AU - Pilowsky, Paul M.
PY - 2003/11/14
Y1 - 2003/11/14
N2 - Anatomical and in vitro studies suggest that mu opioid receptors (MOR) on pre-Bötzinger complex neurons are responsible for opioid induced respiratory depression (Grey et al., Science 286 (1999) 1566). However, mu opioid agonists injected in vivo, in other regions of the ventral respiratory group (VRG), produce respiratory depression, suggesting that opioids are widely distributed in the VRG. We therefore re-examined the distribution of the MOR in the ventral medulla and found MOR-immunoreactive neurons and terminals in all subdivisions of the VRG. Furthermore, we determined, in rats, the effects of a MOR agonist (endomorphin-1, 10 mM, 60 nl, unilateral), microinjected into different subdivisions of the VRG, on phrenic nerve activity. Endomorphin-1 produced changes in phrenic nerve frequency and amplitude, throughout the VRG. Unexpectedly, endomorphin-1 microinjected into the Bötzinger and pre-Bötzinger complexes consistently increased phrenic nerve frequency. These results support the widespread distribution of MOR in the VRG and also indicate that endomorphin-1, a postulated endogenous ligand, may differentially regulate respiration.
AB - Anatomical and in vitro studies suggest that mu opioid receptors (MOR) on pre-Bötzinger complex neurons are responsible for opioid induced respiratory depression (Grey et al., Science 286 (1999) 1566). However, mu opioid agonists injected in vivo, in other regions of the ventral respiratory group (VRG), produce respiratory depression, suggesting that opioids are widely distributed in the VRG. We therefore re-examined the distribution of the MOR in the ventral medulla and found MOR-immunoreactive neurons and terminals in all subdivisions of the VRG. Furthermore, we determined, in rats, the effects of a MOR agonist (endomorphin-1, 10 mM, 60 nl, unilateral), microinjected into different subdivisions of the VRG, on phrenic nerve activity. Endomorphin-1 produced changes in phrenic nerve frequency and amplitude, throughout the VRG. Unexpectedly, endomorphin-1 microinjected into the Bötzinger and pre-Bötzinger complexes consistently increased phrenic nerve frequency. These results support the widespread distribution of MOR in the VRG and also indicate that endomorphin-1, a postulated endogenous ligand, may differentially regulate respiration.
KW - Brainstem
KW - Control of breathing
KW - Mammals
KW - Mu opioid
KW - Mu opioid receptors
KW - Pre-Bötzinger region
KW - Rat
KW - Receptors
KW - Respiratory depression
UR - http://www.scopus.com/inward/record.url?scp=0242522250&partnerID=8YFLogxK
U2 - 10.1016/S1569-9048(03)00173-3
DO - 10.1016/S1569-9048(03)00173-3
M3 - Article
C2 - 14609508
AN - SCOPUS:0242522250
SN - 1569-9048
VL - 138
SP - 165
EP - 178
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
IS - 2-3
ER -