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cAMP‐dependent reversal of opioid‐ and prostaglandin‐mediated depression of the isolated respiratory network in newborn rats
Author(s) -
Ballanyi K.,
Lalley P. M.,
Hoch B.,
Richter D. W.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.127bf.x
Subject(s) - opioid , respiratory system , prostaglandin , depression (economics) , medicine , prostaglandin e2 , endocrinology , prostaglandin f , anesthesia , pharmacology , receptor , economics , macroeconomics
1 Membrane potential ( V m ) and resistance ( R m ) of ventral respiratory group (VRG) neurons were measured in the isolated brainstem–spinal cord from newborn rats during bath application of the opioid receptor agonists fentanyl or [D‐Ala 2 , D‐Leu 5 ]‐enkephalin (Ala‐Leu‐Enk) and of the prostaglandin E t (PGE 1 ). 2 PGE 1 (0.1–3 μ m ) and fentanyl or Ala‐Leu‐Enk (1–50 μ m ) produced depression and, at higher doses, block of inspiratory nerve activity and respiration‐related postsynaptic potentials. This apnoea was associated with hyperpolarization and R m fall in 25% of thirty‐two VRG neurons tested, whereas resting V m and R m were not changed in the other cells. 3 The selective μ‐ and δ‐receptor blockers naloxonazine (10–20 μ m ) and naltrindole (50–100 μ M) antagonized the effects of 5 μ m fentanyl and 50 μ M Ala‐Leu‐Enk, respectively. 4 Opioid‐ and PGE 1 ‐evoked respiratory depression was reversed upon elevation of endogenous cAMP levels by stimulating adenylyl cyclase with 100 μ M forskolin, activating dopamine D 1 receptors with 50–100 μ m 6‐chloro‐7,8‐dihydroxy‐3‐allyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (6‐chloro‐APB) or preventing cAMP breakdown with 50–100 μ m isobutylmethylxanthine. 5 The results indicate that opioid‐ or prostaglandin‐induced respiratory depression is due to a fall in cAMP levels in cells responsible for generation of rhythm or providing a tonic drive to the respiratory network. 6 We suggest that elevation of cAMP levels is an effective antidote in neonates against such forms of respiratory depression.