Desensitization of melanotropin receptors in COS-7 cells.
Non-transfected COS-7 cells have been found to possess functional melanotropin receptors on their cell surface. These receptors, and the properties of the melanocyte stimulating hormone (MSH) peptides can be characterized by measuring melanotropin stimulation of cAMP accumulation in the cells. In these cells we studied the ultra-long lasting super agonist [Nle(4)-D-Phe(7)]-alpha-MSH (NDP-alpha-MSH), and compared it with the endogenous MSH peptides with respect to potency, maximal activity, duration of action, and rate of desensitization. Surprisingly, NDP-alpha-MSH did not act as a full agonist in COS-7 cells. In multiple experiments, it could stimulate cAMP accumulation to approximately 50% of the level of alpha-MSH, beta-MSH and adrenocorticotropic hormone (ACTH). The MSH receptor mediating this activity is unknown. The time course of cAMP accumulation, and the duration of receptor activation was also investigated. In contrast to other systems NDP-alpha-MSH did not induce prolonged activity, with respect to cAMP accumulation, in COS-7 cells. The MSH receptors present in COS-7 were found to desensitize rapidly subsequent to pretreatment by any of the MSH peptides. As expected for a partial agonist, the activity of NDP-alpha-MSH desensitized more rapidly than any of the full agonists. Surprisingly, desensitization induced by pretreatment with NDP-alpha-MSH also occurred more rapidly than desensitization induced by the other MSH analogs.
Polgar
W E
WE
Department of Neuroscience, SRI International, Menlo Park, CA 94025, USA.
Bitler
C M
CM
Toll
L
L
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D000882:Haplorhini; D007668:Kidney / Q000166:cytology / Q000648:ultrastructure*; D009074:Melanocyte-Stimulating Hormones / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000819:agonists / Q000187:drug effects*; D012680:Sensitivity and Specificity; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology
D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP