SP-INDUCED CONTRACTION OF AIRWAY SMOOTH-MUSCLE IN NORMAL AND ALLERGEN-SENSITIZED RABBITS - MECHANISM OF ACTION

We studied the mechanisms involved in the airway smooth muscle (ASM) c ontraction to substance P (SP) in normal (control) and allergen-sensit ized (immune) rabbits as well as immune rabbits exposed to allergen vi a the airways (immune challenged). Cumulative concentration-response c urves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segment s in the absence and presence of atropine (10(-5) M) in vitro. The max imal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means /- SE. We found no difference in the contractile response to SP betwee n control and immune animals. ASM segments obtained from immune-challe nged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contr action at 10(-4) M SP in all three groups; this effect, however, was g reater in immune-challenged tissues. These findings demonstrate an inc reased contractile response to SP in immune-challenged animals mediate d by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a compl ex interaction between direct effects on ASM and indirect effects thro ugh modulation of cholinergic neurotransmission.