title: Mu-opioid receptors in the caudomedial NTS are critical for respiratory responses to stimulation of bronchopulmonary C-fibers and carotid body in conscious rats.
abstract: We tested the hypothesis that mu-opioid receptors (MORs) in the caudomedial nucleus tractus solitarius (cmNTS) are important for the ventilatory responses to stimulation of bronchopulmonary C-fibers (PCFs), the carotid body-mediated hypoxia, and hypercapnia independent of the carotid body. First, we used immunohistochemistry to map MORs distribution in the caudal medulla. Then we compared the effects of intra-cmNTS microinjection of DAMGO (a MOR agonist) with or without a combination of CTAP (a MOR antagonist) on the ventilatory responses to: 1) right atrial injection of capsaicin (to stimulation of PCFs) and 2) acute hypoxia (HVR, to stimulate the carotid body) in awake intact rats; and 3) hypercapnia (HCVR) in the carotid body ablated rats. The cmNTS presented the highest MORs in the caudal medulla. Microinjection of DAMGO blocked the PCF-mediated apnea, attenuated HVR (70%) and HCVR (21%), while microinjection of CTAP+DAMGO failed to affect these chemoreflexes. Our data demonstrate a critical role of activation of cmNTS MORs in regulating these chemoreflexes and imply a presence of MORs in the synapse of the 2nd-order neurons receiving inputs from PCFs and the carotid body, and NTS chemosensitive neurons.
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Gao
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States.
authors.forename: Franklin
authors.initials: F
authors.lastname: Gao
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, United States. Electronic address: fxu@lrri.org.
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006935:Hypercapnia / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000889:Anti-Arrhythmia Agents; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002245:Carbon Dioxide
keywords: Anesthesia; Chemoreception; Opioid; Respiration