Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output.
Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 microM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.
Mutoh
T
T
Departments of Internal Medicine and Pharmacology, University of California, Davis, Sacramento, California 95616, USA.
Bonham
A C
AC
Joad
J P
JP
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000294:innervation*; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000294:innervation*; D008297:Male; D008845:Microinjections; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P; D002211:Capsaicin; C066892:CP 96345