Effects of CP-99,994, an NK1-receptor antagonist, on the inward current produced by substance P.

Immunoreactivities of mammalian tachykinins have been widely demonstrated in the peripheral and central nervous systems (Ogawa et al. 1985; Leeman et al. 1991; Otsuka and Yoshioka, 1993). Dalsgaard et al. (1985) reported the co-existence of substance P(SP) and neurokinin A (NKA)-like immunoreactivities in neurons of rat dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. Recently, molecular cloning of cDNAs revealed three distinct types of tachykinin receptors, NK1, NK2 and NK3, that belong to the GTP binding protein-coupled receptor superfamily (Masu et al. 1987; Hershey and Krause, 1990; Shigemoto et al. 1990). Electrophysiological studies demonstrated that NKA and neurokinin B (NKB) depolarized the neuronal membrane of sympathetic ganglia (Saria et al. 1985; Konishi et al. 1992). Under voltage-clamp conditions, application of SP and NKA produced inward currents that underlie the tachykinin-induced depolarizations in neurons of the bullfrog DRG (Ishimatsu, 1994). The purpose of the present study is to examine the receptor type for SP that produces the inward current in bullfrog DRG cells by using newly identified non-peptide antagonists (Snider et al. 1991; McLean et al. 1993; Watson and Girdlestone, 1994).