Desensitization of melanotropin receptors in COS-7 cells.
Polgar. W E WE; Bitler. C M CM; Toll. L L
Key Findings
- COS-7 cells naturally express functional melanotropin receptors.
- NDP‑alpha‑MSH acts as a partial agonist, producing ~50% of the cAMP response of natural MSH peptides.
- All MSH peptides cause rapid receptor desensitization in COS-7 cells, with NDP‑alpha‑MSH desensitizing the fastest.
Practical Outcomes
- The study hints that frequent melanotan‑I dosing could lead to rapid tolerance, so spacing out doses or cycling might help maintain effectiveness. However, because the work was done in a non‑human cell line, the findings may not fully translate to human skin or systemic use, so apply the insight cautiously.
Summary
In a lab cell line (COS-7), the synthetic peptide melanotan‑I (NDP‑alpha‑MSH) only triggers about half the signaling response of natural hormones and makes the receptors become unresponsive faster than the natural versions. This shows that melanotan‑I is a partial activator and that its effects may wear off quickly with repeated use, at least in this cell model.
Abstract
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.
Study Information
pubmed
1996
1996-03-08T00:00:00.000Z
10.1016/0024-3205(96)00083-5
5
15