Agonist-induced substance P receptor down-regulation in rat central nervous system.

Rat brain slices were incubated with substance P (SP), and the SP receptors on the membranes from those slices were characterized by a 3H-SP binding technique. The number of substance P receptors measured in the extensively washed membrane preparations pretreated with 3 x 10(-5) M SP was reduced by 30% compared with that in nontreated membranes. This reduction was dependent on the incubation time and temperature. The metabolic inhibitors sodium azide and 2,4-dinitrophenol protected SP receptors from the reduction. The characteristics of 3H-SP incorporation into rat brain slices were similar to those of SP receptor down-regulation, that is, the 3H-SP incorporation was time, temperature, and energy dependent. Thus these results indicate that the processes of ligand incorporation and receptor down-regulation are closely associated phenomena. These observations may be important in elucidating the phenomenon of SP-induced desensitization.