Elsevier

Life Sciences

Volume 60, Issues 13–14, 21 February 1997, Pages 1105-1112
Life Sciences

The M5 (m5) receptor subtype: Fact or fiction?

https://doi.org/10.1016/S0024-3205(97)00054-4Get rights and content
Under a Creative Commons license
open archive

Abstract

By comparison to the other subtypes of muscarinic receptors, very little is known about the binding properties, locations, mechanisms and physiological functions of the M5 (m5) receptor subtype. Studies of the m5 receptor have been hampered by the lack of m5-selective ligands or antibodies and a source that endogenously expresses predominantly the m5 receptor subtype. We have developed a pharmacological labeling strategy using the non-selective muscarinic antagonist [3H]NMS, in the presence of muscarinic antagonists and toxins in green mamba venom to occlude the m1-m4 receptor subtypes, to selectively label the m5 receptor subtype. This m5-selective labeling approach, along with those developed for the other four receptor subtypes, has permitted for the first time a comparison of the relative expression levels and anatomical localizations of the five muscarinic receptor subtypes in the brain. The distribution profile of the m5 receptor is distinct from the other four subtypes and is enriched in the outer layers of the cortex, specific subfields of the hippocampus, caudate putamen, olfactory tubercle and nucleus accumbens. These studies have also demonstrated that the levels of m5 receptor protein expression are apparently higher and more widespread than anticipated from previous in situ hybridization and immunoprecipitation studies. Taken together, the results suggest a unique and potentially physiologically important role for the m5 receptor subtype in modulating the actions of acetylcholine in the brain.

Keywords

autoradiography
muscarinic receptors
m5 receptor

Cited by (0)

The nomenclature for muscarinic receptor subtypes has designated the big “M” terminology for the pharmacologically-defined receptors and the small “m” terminology for the molecularly-defined receptors. It is now clear that the ml sequence corresponds to the M1 receptor, the m2 to the M2, etc. Since the receptor subtype-selectivity of the pharmacological labeling strategies described here have been validated using the individual molecular receptors expressed in transfected cells, we have utilized the small “m” terminology to refer to the respective receptors labeled by each of the subtype-selective conditions.