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

• Published in: Pharmaceutical research Vol. 5; no. 12; pp. 795 - 799
• Main Authors: INOUE, A, TAKEDA, R, FUKUYASU, T, NAKATA, Y, SEGAWA, T
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-12-1988
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Brain - drug effects; Brain Chemistry; Central nervous system; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Male; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Neurokinin-1; Receptors, Neurotransmitter - analysis; Receptors, Neurotransmitter - drug effects; Substance P - analysis; Vertebrates: nervous system and sense organs; Desensitization; Radiolabelling; Rat; Substance P; Rodentia; Peptide hormone; Central nervous system; Neuropeptide; Vertebrata; Regulation(control); Mammalia; Radioimmunoassay; Biological receptor
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1015996920198

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.