These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Use of chimeric muscarinic receptors to investigate epitopes involved in allosteric interactions.
    Author: Ellis J, Seidenberg M, Brann MR.
    Journal: Mol Pharmacol; 1993 Sep; 44(3):583-8. PubMed ID: 7690450.
    Abstract:
    All five (m1-m5) muscarinic receptors are sensitive to allosteric regulation, but gallamine is considerably more potent in slowing the dissociation of N-[3H]methylscopolamine (NMS) from the m2 subtype than from the m3 or m5 subtypes. To study the structural basis for the preference of gallamine for the m2 subtype, we evaluated [3H]NMS-gallamine interactions with chimeric receptors in which segments of the m5 receptor were systematically replaced with the corresponding m2 sequence. Substitutions that included the sixth transmembrane domain and third extracellular loop resulted in marked increases in the potency of gallamine, but substitutions that did not include these regions were without effect. A similar substitution was investigated using m2/m3 chimeric receptors, in which a segment extending from the middle of the sixth transmembrane domain to the carboxyl terminus was exchanged. As with the m2/m5 constructs, substitution of the m2 carboxyl-terminal segment into the m3 subtype significantly increased the potency of gallamine. Furthermore, the converse substitution reduced the potency of gallamine dramatically, to approximately that seen for the m3 subtype itself. It appears that this portion of the receptor is a critical determinant for the binding of gallamine and/or the allosteric interactions between gallamine and [3H]NMS.
    [Abstract] [Full Text] [Related] [New Search]