Abstract
Substance P (SubP) and endomorphin-2 (Endo2) are co-localized presynaptically in vesicles of neurons adjacent to inspiratory rhythm-generating pre-Botzinger Complex (preBotC) neurons but the effects of co-released SubP and Endo2 on respiratory motor control are not known. To address this question, SubP alone or a combination of SubP and Endo2 (SubP/Endo2) were bath-applied in a sustained (15-min) or intermittent (5-min application, 5-min washout, x3) pattern at 10-100nM to neonatal rat brainstem-spinal cord preparations. During neuropeptide application, SubP/Endo2 co-applications generally attenuated SubP-induced increases in burst frequency and decreases in burst amplitude. With respect to frequency plasticity (long-lasting increase in burst frequency 60min post-neuropeptide application), SubP-induced frequency plasticity was increased with sustained SubP/Endo2 co-applications at 20 and 100nM. Intermittent SubP/Endo2 co-applications tended to decrease the level of frequency plasticity induced by intermittent SubP alone applications. SubP/Endo2 co-applications revealed potentially new functions for neurokinin-1 (NK1R) and mu-opioid (MOR) receptors on respiratory rhythm-generating medullary neurons.
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