M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord

A. U. Höglund, Helen Baghdoyan

Research output: Contribution to journalArticle

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Abstract

Muscarinic receptors in the spinal cord have been shown to mediate antinociception and alter blood pressure. Currently, there is much interest in identifying which muscarinic receptor subtypes regulate these functions. Toward that end, this study aimed to identify and localize the muscarinic receptor subtypes present in spinal cord using in vitro receptor autoradiography with [3H]-pirenzepine and [3H]-N-methylscopolamine. The results showed that M2 binding sites were distributed throughout the dorsal and ventral horns, whereas M3 binding sites were localized to laminae I to III of the dorsal horn. Only background levels of M1 binding sites were detected. Saturation binding assays using [3H]-pirenzepine in spinal cord homogenates confirmed the absence of M1 receptors. Competition membrane receptor assays using [3H]-N-methylscopolamine and the unlabeled antagonists pirenzepine, 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5, 11- dihydro 6H-pyrido(2,3-b)(1, 4) benzodiazepine-one, methoctramine, and methoctramine in combination with atropine corroborated the autoradiographic findings and also revealed the presence of M4 binding sites. The finding that M2 and M3 binding sites were localized to the superficial laminae of the dorsal horn where nociceptive Aδ and C fibers terminate suggests the possibility that either or both of these muscarinic receptor subtypes modulate antinociception. The present demonstration of M4 binding sites in spinal cord is consistent with the possibility that M2 and/or M4 receptors are involved in the regulation of blood pressure at the spinal level.

Original languageEnglish (US)
Pages (from-to)470-477
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume281
Issue number1
StatePublished - May 24 1997
Externally publishedYes

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Muscarinic M1 Receptors
Spinal Cord
Binding Sites
Muscarinic Receptors
Pirenzepine
N-Methylscopolamine
Blood Pressure
Myelinated Nerve Fibers
Unmyelinated Nerve Fibers
Autoradiography
Atropine
Membranes
Spinal Cord Dorsal Horn

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord. / Höglund, A. U.; Baghdoyan, Helen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 281, No. 1, 24.05.1997, p. 470-477.

Research output: Contribution to journalArticle

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