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Vol. 281, Issue 1, 470-477, 1997
Department of Anesthesia, The Pennsylvania State University,
College of Medicine, Hershey, Pennsylvania
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 A
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.
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