The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat.
We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED50=0.5 microM) on the respiratory rhythm was stronger than NA (ED50=5 microM). The adrenaline respiratory rhythm depression was partially blocked by the alpha1-antagonist prazosin or by the alpha2-antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the alpha1-antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or depressed (n=5 of 39) by adrenaline, and excited by alpha1-agonist phenylephrine or depressed by alpha2-agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA(A)-antagonists bicuculline or picrotoxin, but not by the GABA(B)-antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through alpha-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via alpha1-receptors and inhibition via alpha2-receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA(A)ergic neurons.
Arata
A
A
Department of Physiology, Showa University, School of Medicine, Tokyo, Japan.
Onimaru
H
H
Homma
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists