title: A μ-opioid receptor agonist DAMGO induces rapid breathing in the arterially perfused in situ preparation of rat.
abstract: Ventilatory responses to opioids are complex and not yet fully understood. We evaluated concentration-dependent effects of a selective μ-opioid receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) on respiratory output in the arterially perfused in situ rat preparation, which preserves the integrity of the ponto-medullary respiratory network. DAMGO (300-3400 nM) was added accumulatively to the perfusate. DAMGO increased inspiratory time and diminished central vagal post-inspiratory activity. At 300-500 nM DAMGO caused rapid breathing with shortening of expiratory time. The change of breathing pattern occurred within a single breath. Bilateral vagotomy did not affect the change in respiratory pattern, suggesting that it was of central origin. Additional DAMGO up to 1800 nM did not affect the rapid breathing pattern, and further elevated concentrations (up to 3400 nM) caused inconsistent results. Since the rapid breathing pattern was associated with the obliteration of vagal post-inspiratory activity, we conclude that DAMGO reconfigures the respiratory output to an inspiratory phase-dominant, rapidly alternating inspiration-expiration pattern.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Tadachika
authors.initials: T
authors.lastname: Koganezawa
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okada
authors.forename: Naohito
authors.initials: N
authors.lastname: Terui
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Oku
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists; D012119:Respiration / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-