| First Author | Jain S | Year | 2018 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 315 |
| Issue | 3 | Pages | E357-E366 |
| PubMed ID | 29812984 | Mgi Jnum | J:266037 |
| Mgi Id | MGI:6207452 | Doi | 10.1152/ajpendo.00024.2018 |
| Citation | Jain S, et al. (2018) Melanotan II causes hypothermia in mice by activation of mast cells and stimulation of histamine 1 receptors. Am J Physiol Endocrinol Metab 315(3):E357-E366 |
| abstractText | Intraperitoneal administration of the melanocortin agonist melanotan II (MTII) to mice causes a profound, transient hypometabolism/hypothermia. It is preserved in mice lacking any one of melanocortin receptors 1, 3, 4, or 5, suggesting a mechanism independent of the canonical melanocortin receptors. Here we show that MTII-induced hypothermia was abolished in Kit(W-sh/W-sh) mice, which lack mast cells, demonstrating that mast cells are required. MRGPRB2 is a receptor that detects many cationic molecules and activates mast cells in an antigen-independent manner. In vitro, MTII stimulated mast cells by both MRGPRB2-dependent and -independent mechanisms, and MTII-induced hypothermia was intact in MRGPRB2-null mice. Confirming that MTII activated mast cells, MTII treatment increased plasma histamine levels in both wild-type and MRGPRB2-null, but not in Kit(W-sh/W-sh), mice. The released histamine produced hypothermia via histamine H1 receptors because either a selective antagonist, pyrilamine, or ablation of H1 receptors greatly diminished the hypothermia. Other drugs, including compound 48/80, a commonly used mast cell activator, also produced hypothermia by both mast cell-dependent and -independent mechanisms. These results suggest that mast cell activation should be considered when investigating the mechanism of drug-induced hypothermia in mice. |
