Deletion of Tachykinin NK1 Receptor Gene in Mice does not Alter Respiratory Network Maturation but Alters Respiratory Responses to Hypoxia.

The aim of this study was to shed some light on the role of Substance Ρ (SP) and its neurokinin NK1 receptors (NK1R) in respiratory network maturation and function. On the one hand, as SP is detected early during development (Tsuchida et al., 1990; Beresford et al., 1992; Taoka et al., 1996; St John et al, 1997), SP is assumed to play a role in the early organization of the CNS (Quirion and Dam, 1986) and therefore in that of the respiratory network. On the other hand, compelling evidence exists that activation of NK1R affects ventilation. First, NK1R are expressed within the pre-Botzinger complex, a region containing putative rhythm generating neurons (Gray et al., 1999; Wang et al, 2001) and NK1R activation increases respiratory activity (Hedner et al., 1984; Chen et al., 1990; Yamamoto et al., 1992; Monteau et al., 1996; Ptak et al., 1999, 2000a, b) whereas destruction of NK1R-positive cells alters breathing (Gray et al., 2001). Second, SP may be implicated in the central transmission of the inputs from the carotid bodies (CB) which detect peripheral hypoxia since SP is contained in CB afferent nerves (Liebstein et al, 1985; Lindefors et al., 1986) and in fiber terminals within the nucleus tractus solitarius (Lipski et al., 1977; Mantyh et al., 1989). SP concentration increases within the nucleus tractus solitarius during hypoxia, but not after CB denervation (Srinivasan et al., 1991). Furthermore, lack of the SP degradation enzyme increases SP concentration within nucleus tractus solitarius and enhances the respiratory response to hypoxia (Grasemann et al., 1999).