Substance P and central respiratory activity: a comparative in vitro studyin NK1 receptor knockout and wild-type mice

Neurokinin-1 receptors (NK1) are present within the respiratory medullary n etwork and in the phrenic nucleus, which controls the diaphragm. We compare d the efficacy of substance P (SP) at inducing changes in respiratory frequ ency or the amplitude of the respiratory motor output between NK, knockout (NK1-/-) and wild-type mice, using the in vitro brainstem-spinal cord prepa ration. The in vitro respiratory frequency, as well as the variability of t he rhythm and the amplitude of the motor output were similar in both lines. In wild-type mice, application of exogenous SP induced either an increase in respiratory frequency (superfusion of the medulla) or an increase of the inspiratory motor output, as defined by the integral of C4 cervical ventra l root activity (superfusion of the spinal cord). These two effects were no t apparent in NK1-/- mice. In conclusion, NK1 receptors mediate the respira tory responses to SP but the lack of NK1 receptors in newborn NK1-/- mice d oes not change the respiratory activity.