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| Content Provider | PubMed Central |
|---|---|
| Author | Ruat, M. Körner, M. Garbarg, M. Gros, C. Schwartz, J. C. Tertiuk, W. Ganellin, C. R. |
| Abstract | Aminophenpyramine--i.e., N-(5-[2-(4-aminophenyl)ethanamidopentyl])-N'-(4-methoxybenzyl)-N-m ethyl-N'- (2-pyridinyl)-1,2-ethanediamine, a derivative of mepyramine (pyrilamine), a typical antagonist of histamine at its H1 receptor--was synthesized and converted into [125I)iodoazidophenpyramine, a potential photoaffinity probe for the H1 receptor. In the dark, reversible binding of this probe to cerebellar membranes occurred with a Kd of 1.2 x 10(-11) M and a Bmax of 240 fmol/mg of protein and was inhibited by various H1-receptor antagonists with the expected potencies. These features establish the compound as one of the most potent H1-receptor antagonists known so far. Upon UV irradiation, 5% of the bound radioactivity was covalently incorporated into cerebellar membrane polypeptides as shown by standard NaDodSO4/PAGE. Two bands of 47 and 56 kDa were consistently labeled, labeling being prevented by various H1-receptor antagonists with the expected potencies and stereoselectivity. In the presence of protease inhibitors, labeling of the 56-kDa peptide increased at the expense of the 47-kDa peptide, suggesting that the latter was produced by hydrolysis of the former under the action of membrane proteases. In the absence of 2-mercaptoethanol, a band of 350-400 kDa appeared, apparently at the expense of the lighter bands, suggesting that the latter might be linked by one or more disulfide bridges to a higher molecular mass complex. We propose that at least part of the ligand binding domain of the histamine H1 receptor resides within a subunit of apparent molecular mass 56,000. |
| Starting Page | 2743 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 85 |
| Language | English |
| Publisher Date | 1988-04-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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