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Mu opioid receptors inhibit the exercise pressor reflex by closing N‐type calcium channels but not by opening GIRK in rats.
Author(s) -
Estrada Juan A.,
Kaufman Marc A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.725.5
Subject(s) - damgo , reflex , g protein coupled inwardly rectifying potassium channel , chemistry , agonist , medicine , endocrinology , calcium channel blocker , pharmacology , anesthesia , receptor , calcium , opioid receptor , g protein
Mu opioid G‐protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N‐type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect. In decerebrate rats, we determined the effect of intrathecal injection of either tertiapin LQ, which blocks the GIRK channel or ω‐conotoxin‐GVIA, which blocks the N‐type calcium channel on the exercise pressor reflex which was evoked by contracting the triceps surae muscles. Initially, we established that intrathecal injection of DAMGO, highly selective MOR agonist, inhibited the exercise pressor reflex relative to no intrathecal injection or intrathecal saline injection (P<0.001, n=5). We then found that intrathecal injection of two doses of tertiapin‐LQ (1 and 10 μg), a GIRK blocker, had no effect on the exercise pressor reflex (n=6 and n=7, respectively; P> 0.05). Importantly, neither dose of tertiapin‐LQ prevented the DAMGO‐induced inhibition of the exercise pressor reflex. Last, we found that intrathecal injection of ω‐conotoxin‐GVIA, an N‐type calcium blocker, markedly attenuated the exercise pressor reflex (P<0.001, n=7). The cardioaccelerator response to contraction did not appear to be effected in any of the experiments. We conclude that N‐type voltage‐gated calcium channel inhibition appears to be the mechanism by which MOR activation inhibits the exercise pressor reflex in decerebrate rats. Support or Funding Information This work was supported by NIH grants R01 AR 059397 and P01 HL 134609. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .