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Systems Neurobiology Laboratory, Department of Neurobiology, University of California Los Angeles, Box 951763, Los Angeles, CA 90095, USA
The specific role of the neuromodulator substance P (SP) and its target, the neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory activity is not known. The preBötzinger complex (preBötC), an essential site for respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones that are strongly modulated by exogenously applied SP or acute pharmacological blockade of NK1Rs. We investigated the effects of capsaicin, which depletes neuropeptides (including SP) and glutamate from presynaptic terminals, on respiratory motor output in medullary slice preparations of neonatal rat that generate respiratory-related activity. Bath application of capsaicin slowed respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm could be restored by bath application of SP or glutamate transporter blockers. Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres within the preBötC. Our results suggest that depletion of SP (or other peptides) and/or glutamate by capsaicin causes a cessation of respiratory rhythm in neonatal rat slices.
(Received 23 December 2003;
accepted after revision 8 January 2004;
first published online 14 January 2004)
Corresponding author C. Morgado-Valle: Department of Neurobiology, David Geffen School of Medicine at UCLA, Box 951763, Los Angeles, CA 90095-1763, USA. Email: cmorgado{at}mednet.ucla.edu
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