Cholinergic-opioid interactions at brainstem respiratory chemosensitive areas in cats.
Central respiratory chemosensitivity has been ascribed to CO2-sensitive neurons located on the ventral brainstem surface. The effects of cholinergic mechanisms on CO2-sensitive neuronal activity recorded extracellularly at the brainstem respiratory chemosensitive area at the caudal ventral medullary surface (cVMS) were investigated in cats (n = 14) anesthetized with chloralose-urethane. The neurons increased their firing rate from 10.4 +/- 1.6 Hz to 33.9 +/- 5.2 Hz when the mock cerebrospinal fluid (mCSF) superfusing buffer solution was changed from pH 7.4 (control) to pH 7.0 (acidic). Atropine (ATR) applied topically to the cVMS depressed the H(+)-ion-induced increase in neuronal frequency from 32.8 +/- 4.8 Hz to 13.4 +/- 2.2 Hz. ATR also depressed the inspired-CO2-induced increase in neuronal activity from 33.2 +/- 8.3 Hz to 18.9 +/- 4.9 Hz, suggesting the possibility of a muscarinic cholinergic involvement in cVMS neuronal responses to changes in PCO2 and mCSF-pH. Acetylcholine (ACh) increased the activity of cVMS CO2-sensitive neurons by 237.5% +/- 34.9%, and naloxone applied topically to the cVMS augmented the ACh responsiveness to 338.6% +/- 52.7%. Physostigmine (PHY) increased neuronal activity by 254.3% +/- 42.9%, and this increase was augmented to 435.4% +/- 61.2% by naloxone. Although responses of the CO2-sensitive neurons to PHY were biphasic, the depressant phase failed to appear whenever the cVMS was pretreated with naloxone. Naloxone also augmented the responsiveness of cVMS neurons to increased H+ ion superfusion. These findings suggest that the endogenous opiates may be involved in the central regulation of respiration by interaction with CO2-sensitive cholinergic structures at the cVMS.(ABSTRACT TRUNCATED AT 250 WORDS)
Trouth
C O
CO
Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, D.C. 20059.
Millis
R M
RM
Bernard
D G
DG
Pan
Y
Y
Whittaker
J A
JA
Archer
P W
PW
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002245:Carbon Dioxide / Q000494:pharmacology; D002415:Cats; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004723:Endorphins / Q000502:physiology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*
D004723:Endorphins; D002245:Carbon Dioxide; D009270:Naloxone; D001285:Atropine; D010830:Physostigmine; D000109:Acetylcholine