ATTENUATION OF AGONIST-INDUCED DESENSITIZATION OF THE RAT SUBSTANCE-PRECEPTOR BY PROGRESSIVE TRUNCATION OF THE C-TERMINUS

We have investigated the C-terminal tail of the rat substance P recept or (SPR) as a domain essential for agonist-induced desensitization. Fo ur progressively shorter mutants, using premature termination in the C -terminus, were constructed and compared with the unaltered SPR using ectopic expression of wild-type and mutant receptors in Xenopus oocyte s. These mutants were designated, D16, D47, D70 and D96 with 16, 47, 7 0 and 96 amino acids residues deleted from the tail, respectively. Wil d type SPR, D16 and D47 exhibited normal current responses when challe nged with substance P, but D70 and D96 had reduced maximal current res ponses (70% and 5% of wild type SPR, respectively). D70, however, exhi bited substantial resistance to substance P-induced desensitization in that 55%, versus 8% for wild type SPR, of the peak current of the fir st response was preserved on second challenge with substance P, Theref ore, a domain from residues 338 to 360 of the rat SPR, though not nece ssary for the functional activity of the receptor, plays an essential role in agonist-induced desensitization.