Effect of substance P on respiratory rhythm and pre-inspiratory neurons in the ventrolateral structure of rostral medulla oblongata: an in vitro study.

The pre-inspiratory (Pre-I) neurons which fire in the pre- and usually also during the post-inspiratory phase are located in the ventrolateral structures of the rostral medulla. They are suggested as primary rhythm generating neurons for respiration. These have been studied in isolated brainstem-spinal cord preparations from newborn 0-5-day-old rats. We have found that application of substance P (SP) enhanced the respiratory rhythm as measured by C4 ventral root and pre-I neuronal activities. Furthermore, the effect of SP was dependent on basal respiratory rate. An increase of the Pre-I and C4 burst rate by SP was clearer when the basal respiratory rhythm was somewhat lower. Moreover, long lasting depression of respiratory rate after the application of the alpha 2-agonist clonidine was reversed by SP. On the other hand, an inhibitory effect appeared in preparations with a higher basal respiratory rate, while the Pre-I burst rate tended to increase during SP perfusion. During chemical synaptic transmission blockade by perfusion with low Ca2+, high Mg2+ solution, a pre-I burst retained or completely blocked was found to be enhanced or reactivated by SP perfusion. The results suggest a direct postsynaptic action of SP, which could strongly stimulate burst generating properties of Pre-I neurons.