fulltext.study @t Gmail

Activation of membrane receptors by a neurotransmitter conjugate designed for surface attachment

Paper ID Volume ID Publish Year Pages File Format Full-Text
12381 791 2005 9 PDF Available
Title
Activation of membrane receptors by a neurotransmitter conjugate designed for surface attachment
Abstract

The derivatization of surfaces with bioactive molecules is a research area of growing importance for cell and tissue engineering. Tetherable molecules used in such applications must contain an anchoring moiety as well as the biofunctional group, typically along with a spacer to prevent steric clashes between the target molecule and the tethering surface. Post-synaptic membrane receptors at chemical synapses in neural tissue mediate signaling to the post-synaptic neuron and are activated by the binding of diffusible neurotransmitter molecules released by the pre-synaptic neuron. However, little attention has been directed at developing neurotransmitter analogs that might retain functionality when tethered to a surface that could be interfaced with post-synaptic receptor proteins. Muscimol (5-aminomethyl-3-hydroxyisoxazole), an analog of GABA (γ-aminobutryic acid), is a known potent agonist of GABAA and GABAC post-synaptic receptors found in retina and other central nervous system tissue. The present paper reports experiments testing the electrophysiological activity of “muscimol-biotin” on cloned GABA receptors expressed in Xenopus oocytes. This compound, which is potentially suitable for tethering at avidin-coated surfaces, consists of muscimol conjugated through an N-acyl linkage to a 6-aminohexanoyl chain that is distally terminated by biotin. We find that muscimol-biotin, as well as a structurally similar compound (muscimol-BODIPY®) containing a bulky fluorophore at the distal end of the aminohexanoyl chain, exhibits substantial agonist activity at GABAA and GABAC receptors. Muscimol-biotin and other similarly biotinylated neurotransmitter analogs, in combination with surface functionalization using avidin-biotin technology, may be useful in applications involving the controlled activation of neuronal post-synaptic receptors by surface-attached molecules.

Keywords
Neurotransmitter; GABA receptor; Muscimol; Biotin; BODIPY®; Nerve tissue engineering; Electrophysiology
First Page Preview
Activation of membrane receptors by a neurotransmitter conjugate designed for surface attachment
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 26, Issue 14, May 2005, Pages 1895–1903
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us