title: Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).
abstract: The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.
authors.affiliation: Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Jørgensen
authors.affiliation: Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Krogh-Jensen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Darryl S
authors.initials: DS
authors.lastname: Pickering
authors.affiliation: School of Agricultural and Veterinary Sciences, South Eastern Kenya University, P.O. BOX 170-90200, Kitui, Kenya.
authors.forename: Titus I
authors.initials: TI
authors.lastname: Kanui
authors.affiliation: Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamvej 3B, 2200, Copenhagen, Denmark. klasab@sund.ku.dk.
authors.forename: Klas S P
authors.initials: KS
authors.lastname: Abelson
mesh_terms: D000818:Animals; D005260:Female; D005557:Formaldehyde; D008297:Male; D019577:Mole Rats / Q000235:genetics / Q000502:physiology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D019832:N-Methylscopolamine; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013830:Thiadiazoles / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014316:Tritium
chemical_list: C579414:3-amino-N-(4-methoxybenzyl)-4,6-dimethylthieno(2,3-b)pyridine-2-carboxamide; D018721:Muscarinic Agonists; D011725:Pyridines; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic; D013830:Thiadiazoles; D013876:Thiophenes; D014316:Tritium; D005557:Formaldehyde; C075257:xanomeline; D019832:N-Methylscopolamine
keywords: Cholinergic receptors; Muscarinic, antinociception, formalin test; Naked mole-rat