Pharmacological properties of whale shark (Rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: Interaction with MRAP1 and MRAP2
GENERAL AND COMPARATIVE ENDOCRINOLOGY
Authors: Hoglin, Brianne E.; Miner, Marin; Dores, Robert M.
Abstract
In the current study, the whale shark (ws; Rhincodon typus) melanocortin-2 receptor (MC2R) co-expressed with wsMRAP1 in Chinese Hamster Ovary (CHO) Cells could be stimulated in a dose dependent manner by ACTH(1-24) with an EC50 of 2.6 x 10(-10) M +/- 9.7 x 10(-11). When the receptor was expressed alone, stimulation was only observed at [10(-6) M]. A comparable increase in sensitivity to stimulation by srDes-Ac-alpha MSH was also observed when the receptor was co-expressed with wsMRAP1. In addition, co-expression with wsMRAP1 significantly increased the trafficking of wsMC2R to the plasma membrane of CHO cells. Surprisingly, co-expression with wsMRAP2 also increased sensitivity to stimulation by ACTH(1-24) and srDes-Ac-alpha MSH, and increased trafficking of the receptor to the plasma membrane. These observations are in sharp contrast to the response of MC2R orthologs of bony vertebrates which have an obligate requirement for co-expression with MRAP1 for both trafficking to the plasma membrane and activation, and while co-expression with MRAP2 increases trafficking, it has minimal effects on activation. In addition, when comparing the activation features of wsMC2R with those of the elephant shark MC2R and red stingray MC2R orthologs, both similarities and differences are observed. The spectrum of features for cartilaginous fish MC2R orthologs will be discussed. A second objective of this study was to determine whether wsMC5R has features in common with wsMC2R in terms of ligand selectivity and interaction with wsMRAP paralogs. While wsMC5R can be activated by either srACTH(1-24) or srDes-Ac-alpha MSH, and co-expression with wsMRAP1 enhances this activation, wsMRAP1 had no effect on the trafficking of wsMC5R. Co-expression with wsMRAP2 had no positive or negative effect on either ligand sensitivity or trafficking of wsMC5R.
A Single-center Randomized Clinical Trial Comparing the Treatment Efficacy of High Dose Oral Prednisolone with Intramuscular Adrenocorticotropic Hormone in Patients with Infantile Spasm
INTERNATIONAL JOURNAL OF PEDIATRICS-MASHHAD
Authors: Imannezhad, Shima; Akhondian, Javad; Ashrafzadeh, Farah; Toosi, Mehran Beiraghi; Hashemi, Narges; Emadzadeh, Maryam; Akhondian, Mohammad Reza
Abstract
Background Infantile spasm is a rare condition in infants from 4 to 7 months old. Treatment varies in different cases. Corticosteroids and adrenocorticotropic hormone (ACTH) are the most widely used treatment options; however, there are debates on their efficacy. The aim of our study is to compare corticosteroid treatment with ACTH in patients with infantile spasm. Materials and Methods: In a randomized clinical trial, 51 patients with infantile spasm were enrolled in the study and distributed into two groups, including the corticosteroid (twenty-six patients), and ACTH (twenty-five patients) groups. The patients in the corticosteroid group received a dose of 8 mg/kg/day (max: 60 mg) of prednisolone in three divided doses for three weeks, and the dose was later tapered in responders. Non-responders after two weeks received 2-3 U/kg/day of ACTH (max: 100 U) for five days. The outcome was assessed using EEG and clinical remission of the disease. The comparison of the two groups was made using SPSS software version 20.0. Results: Twenty-six patients were treated with prednisolone and 25 patients with ACTH. There was no significant difference in gender, age, age of seizure onset, and growth abnormalities. At the end of the study, 13 patients in the prednisolone group and 17 patients in the ACTH group had normal EEG rhythm with no significant difference (p=0.33). As to clinical response, 18 patients in the prednisolone group (69.2%), and 19 in the ACTH group (76%) responded to treatment with no significant difference regarding the treatment outcome (p=0.58). Conclusion There was no considerable difference regarding treatment of infantile spasm with high dose prednisolone or ACTH in in this study.