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

Abstract.

Neurokinin-1 receptors (NK₁) are present within the respiratory medullary network and in the phrenic nucleus, which controls the diaphragm. We compared the efficacy of substance P (SP) at inducing changes in respiratory frequency or the amplitude of the respiratory motor output between NK₁ knockout (NK₁ ^–/–) and wild-type mice, using the in vitro brainstem-spinal cord preparation. The in vitro respiratory frequency, as well as the variability of the 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 ventral root activity (superfusion of the spinal cord). These two effects were not apparent in NK₁ ^–/– mice. In conclusion, NK₁ receptors mediate the respiratory responses to SP but the lack of NK₁ receptors in newborn NK₁ ^–/– mice does not change the respiratory activity.