Detail of "2361-96-8"

Reference

Chymotrypsin substrate analogs inhibit endocytosis of insulin and insulin receptors in adipocytes

Chymotrypsin substrate analogs inhibit endocytosis of insulin and insulin receptors in adipocytes. Jochen, Albert L.; Berhanu, Paulos (Health Sci. Cent., Univ. Colorado, Denver, CO 80262, USA). J. Cell Biol. 58690-81-6 and 9004-10-8 are cas registry numbers. These chemicals are also mentioned in this article., 103(5, Pt. 1), 1807-16 (English) 1986. CODEN: JCLBA3. ISSN: 0021-9525. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) To explore the possible role of proteolytic step(s) in receptor-mediated endocytosis of insulin [9004-10-8], the effects of inhibitors of various classes of proteases on the internalization process were studied in isolated rat adipocytes. Intracellular accumulation of receptor-bound 125I-insulin at 37° was quantitated after rapidly dissocg. surface-bound insulin with an acidic buffer (pH 3.0). Of the 23 protease inhibitors tested, only chymotrypsin [9004-07-3] substrate analogs inhibited insulin internalization. Internalization was decreased 62-90% by 5 different chymotrypsin substrate analogs: N-acetyl-Tyr Et ester [840-97-1], N-acetyl-Phe Et ester [2361-96-8], N-acetyl-Tyr Et ester [2382-80-1], benzoyl-Tyr Et ester [3483-82-7], and benzoyl-Tyr amide [58690-81-6]. The effect of the substrate analogs in inhibiting insulin internalization was dose-dependent, reversible, and required the full structural complement of a chymotrypsin substrate analog. Cell surface receptor no. was unaltered at 12°. However, concomitant with their inhibition of insulin internalization at 37°, the chymotrypsin substrate analogs caused a marked increase (160-380%) in surface-bound insulin, indicating trapping of insulin-receptor complexes on the cell surface. Addnl., 1 mM N-acetyl-Tyr Et ester decreased overall insulin degrdn. by 15-20% and also prevented the chloroquine-mediated increase in intracellular insulin, further indicating that surface-bound insulin was prevented from reaching intracellular chloroquine-sensitive degrdn. sites. The internalization of insulin receptors that were photoaffinity labeled on the cell surface with B2(2-nitro-4-azidophenylacetyl)-des-PheB1-insulin was also inhibited 70-90% by the 5 chymotrypsin substrate analogs, as detd. by the effects of the analogs on the accumulation of trypsin-insensitive (intracellular) 440 kilodalton intact labeled receptors. Thus, chymotrypsin substrate analogs efficiently inhibit the internalization of insulin and insulin receptors in adipocytes and implicate a possible role for endogenous chymotrypsin-like enzyme(s) or related substances in receptor-mediated endocytosis of insulin. .

Selective inhibition of the insulin-stimulated phosphorylation of the 95,000 dalton subunit of the insulin receptor by TAME or BAEE

Selective inhibition of the insulin-stimulated phosphorylation of the 95,000 dalton subunit of the insulin receptor by TAME or BAEE. Tamura, Shinri; Schwartz, Charles F. W.; Whipple, Judith H.; Dubler, Robert E.; Fujita-Yamaguchi, Yoko; Larner, Joseph (Sch. Med., Univ. Virginia, Charlottesville, VA 22908, USA). Biochem. Biophys. Res. Commun.Several substances with their cas registry numbers 2364-87-6 and 7244-67-9 may be metioned in this study., 119(2), 465-72 (English) 1984. CODEN: BBRCA9. ISSN: 0006-291X. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Added Na-p-tosyl-L-arginine Me ester (TAME) [901-47-3] or Na-benzoyl-L-arginine Et ester (BAEE) [971-21-1] inhibited the stimulation by insulin [9004-10-8] of phosphorylation of the 95,000 dalton subunit of the insulin receptor, both in a partially purified fraction from rat adipocytes and in a highly purified prepn. from human placenta. Na-p-Tosyl-L-lysine chloromethyl ketone [2364-87-6], Na-p-tosyl-L-lysine Me ester [6072-04-4], or N-acetyl-L-phenylalanine Et ester [2361-96-8] were much less potent, whereas N-benzoyl-L-alanine Me ester [7244-67-9] was without effect. Inhibition of the phosphorylation by the arginine analogs did not require preincubation of the insulin receptor with inhibitors in the presence of insulin prior to phosphorylation. Inhibition by TAME was decreased by preincubation of the receptor fraction with unlabeled ATP [56-65-5] and MnCl2. Evidently, TAME inhibits an initial ATP- and Mn2+-dependent reaction in the insulin-stimulated phosphorylation process. .