N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice.

N-terminal fragments of substance P (SP) were tested for antagonism against the aversive responses induced in mice by various tachykinin receptor agonists, somatostatin and bombesin. When co-administered with SP intrathecally, low doses (1.0-4.0 pmol) of SP (1-7) or SP (1-8) reduced the SP-induced behavioural responses of scratching, biting and licking. Aversive responses induced by two other neurokinin (NK) 1 receptor agonists, Septide and physalaemin, were also dose-dependently decreased by the simultaneous injection of small doses of SP (1-7) or SP (1-8). Aversive responses induced by 400 pmol of NK A were also significantly reduced by co-administration of SP (1-7) or SP (1-8). No significant effects of the N-terminal fragments were observed against the aversive responses elicited by NK A (300 pmol), eledoisin, NK B, somatostatin or bombesin. These results suggest that the behavioural antagonism produced by SP (1-7) and SP (1-8) may be limited to the NK 1 receptor at the spinal level in mice.