Substance P receptor function in the rat with septic encephalophathy

Substance P(SP) receptor in the brain and spinal cord was examined in the rat with septic encephalopathy produced by cecal ligation and puncture. After surgical procedures, the septic rats became lethargic and their behaviors evaluated by open-field method were depressed and pain threshold tsted by tail-flick method was increased with time (n＝17). For ecaluation of substance P receptor function, distribution of specific binding sites of [^<125>I]-Bolton Hunter SP was determined in 22 descrete brain regions, using in vitro autoradiography. Brain smaples were taken when the septic rats showed full development of septic encephalopathy 11 (±1) hours after the surgical procedures. The sham-operated rats (n＝16) were decapitated at the same time. Binding sites of SP in septic rats were significantly decreased to 70, 50, 60, 70, 70, 80, 60, 40% and 70% of sham-operated rats in ant. cinglate, caudate-outamen (C-P), globus pallidus, hippocampus (HIP), amyhdala (AMY), septal n. (SEP), interpeduncular n. (INT), dorsal raphe (RAP) and cerebellum, respectively. For more questitative description, the number of receptors (Bmax) and affinity consant (Ka) were calculated with the Scatchard analysis in representative SP systems. When compared the septic rats with the sham-operated rats, the Bmax decreased to 60-80% in C-P, HIP, AMY, SEP, INT and RAP wihle Ka increased to 130-220% in C-P, HIP, INT and spinal cord. These resuluts suggest that septic encephalopathy is associated with decreased sensitivity to SP in the brain. This study is the first demonstrarion of the changes in SP receptor function in the septic rat.