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γ-MSH Peptides in the Pituitary
| Content Provider | Scilit |
|---|---|
| Author | Denef, C. Lu, J. Swinnen, E. |
| Copyright Year | 2003 |
| Description | Journal: Annals of the New York Academy of Sciences The melanocortin (MC) gamma3-MSH is believed to signal through the MC3 receptor. We showed that it induces a sustained increase in intracellular free calcium levels ([Ca(2+)](i)) in a subpopulation of pituitary cells. Most of the cells responding to gamma3-MSH express more than one pituitary hormone mRNA. The effect of gamma3-MSH is blocked by SH鄙, a MC3R and MC4R antagonist, in only 50% of the responsive cells, suggesting that in half of these cells the mediating receptor is not the MC3R. Low picomolar doses of gamma3-MSH increase [Ca(2+)](i) in the growth hormone (GH)- and prolactin (PRL)-secreting GH3 cell line. gamma2-MSH and alpha-MSH display a similar effect. SH鄙 does not affect the gamma3-MSH-induced [Ca(2+)](i) response. MTII, a potent synthetic agonist of the MC3R, MC4R, and MC5R, also shows no or low potency in increasing [Ca(2+)](i). By means of RT-PCR, the mRNA of the MC2R, MC3R, and MC4R receptors is undetectable. Experiments testing gamma2-MSH analogues with single alanine replacements show that, unlike the classic MCRs, the His(5)-Phe(6)-Arg(7)-Trp(8) sequence in gamma2-MSH is not a core sequence for activating the gamma-MSH receptor in GH3 cells, whereas Met(3) is essential. Low nanomolar doses of gamma-MSH increase intracellular cAMP levels. Blockade of protein kinase A abolishes the [Ca(2+)](i) responses to gamma3-MSH. gamma2-MSH increases binding of [S(35)]GTPgammaS to membrane preparations of GH3 cells. The pharmacological characteristics of gamma-MSH peptides and analogues on [Ca(2+)](i) and the signal-transduction pathways present strong evidence for the expression of a hitherto uncharacterized gamma-MSH receptor in GH3 cells, belonging to the G protein-coupled receptor family. |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2003.tb03171.x/pdf |
| Ending Page | 132 |
| Page Count | 10 |
| Starting Page | 123 |
| e-ISSN | 17496632 |
| DOI | 10.1111/j.1749-6632.2003.tb03171.x |
| Journal | Annals of the New York Academy of Sciences |
| Issue Number | 1 |
| Volume Number | 994 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2003-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Annals of the New York Academy of Sciences Endocrinology and Metabolism Single‐cell Rt‐pcr Melanocortin Receptors |
| Content Type | Text |
| Resource Type | Article |