Mechanisms Of Itch Evoked By The Muscle Building Supplement Beta-alanine
Qin Liu Medicine & Science in Sports & Exercise Volume 45, May 2013, Supplement 1 5S, p 185
Beta-alanine is one of the few naturally occurring beta amino acids occurring in humans. In combination with L-histidine, beta-alanine forms the dipeptide carnosine found in high
concentrations in several tissues including muscle where it functions as an intracellular buffer. Beta-alanine is a widely used as a dietary supplement to increase intramuscular carnosine
synthesis, in an attempt to improve exercise performance by delaying the onset of pH induced peripheral muscle fatigue. The most common side effect of beta-alanine is a tingling of the skin
and itch which is apparent above a single dose of 10mg per kg body mass, although symptoms may be attenuated with higher doses where a sustained release formulation of beta-alanine is
PURPOSE: To determine the underlying molecular mechanism responsible for the symptoms of tingling and itch.
RESULTS: Beta-alanine is a putative ligand for several receptors including MrgprD, a G protein-coupled receptor specifically expressed in a subpopulation of primary sensory neurons that
exclusively innervate skin. Using mouse behavioral assays and human psychophysical data we have been able to demonstrate that beta-alanine’s site of action is the skin and that MrgprD
receptors are required for beta-alanine induced itch. In vivo electrophysiological recording and in vitro Ca2+ imaging show that a highly restricted subset of MrgprD+ DRG neurons is directly
activated by beta-alanine. This subset is mechanically sensitive and completely segregated from the histamine-responsive population, and may be the long-sought mechanically sensitive itchdetecting
CONCLUSION: MrgprD functions as an itch receptor and mediates non-histaminergic itch induced by beta-alanine. The primary sensory neurons responsive to beta-alanine are likely part of
a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines.
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