期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 295, 期 1, 页码 R243-R251出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00184.2008
关键词
opioid receptors; GABA(B) receptors; neurokinin receptors; control of breathing; airway defensive reflexes
类别
We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii ( NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [D-Ala(2), N-Me- Phe(4), Gly(5)-ol]-enkephalin ( DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed ( 5 mM and 1 mM, respectively). DAMGO ( 0.5 mM) and baclofen ( 0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists ( 10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 ( 10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 ( 5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.
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