Neurokinin-1 versus mu-opioid receptor binding in rat nucleus tractus solitarius after single and recurrent intermittent hypoxia

Abstract

G protein-coupled excitatory neurokinin-1 and inhibitory mu-opioid receptors exist in respiratory brainstem with their peptides and influence breathing. To assess their putative role in respiratory responses to hypoxia, neurokinin-1, and mu-opioid receptor binding was determined in the respiratory nucleus tractus solitarius of the mature rat after single and recurrent intermittent hypoxia versus normoxia. Hypoxia comprised six 5-min bouts of 8% O 2–92% N 2 interceded by 5-min bouts in 21% O 2–79% N 2 (normoxia), either on 6 consecutive days (recurrent intermittent hypoxia) or on the 6th day only (single intermittent hypoxia). Controls comprised six daily sessions in normoxia. To examine the plasticity in receptor response, brains were collected 5 min, 2 h, or 24 h after the last gaseous exposure. Sections from each brainstem underwent quantitative film autoradiography with iodinated substance P and DAMGO for neurokinin-1 and mu-opioid receptors, respectively. Neurokinin-1 receptor binding decreased 5 min after single and recurrent hypoxia and 2 h after recurrent hypoxia, whereas mu-opioid binding remained unchanged. The binding of both receptors increased 24 h after recurrent intermittent hypoxia. Neurokinin versus mu-opioid binding differences immediately posthypoxia might affect physiological responses to episodic hypoxia.