Cholinergic deafferentation of dorsal hippocampus by fimbria-fornix lesioning differentially regulates subtypes (m1-m5) of muscarinic receptors.
Unilateral aspiration lesions of the rostral supracallosal stria/cingulum bundle and fimbria-fornix were performed on adult female rats. Ten and 24 days post lesioning, an elevation (17%; p < 0.01) of total muscarinic receptors was observed in lesioned versus control hippocampi. By using antisera selective for each of the five molecularly defined subtypes (m1-m5) of muscarinic receptors, significant changes were observed in the levels of expression for at least four receptor proteins. Three receptor subtypes increased in density: m1 by 14% (from 943 to 1,078 fmol/mg); m3 by 77% (from 150 to 268 fmol/mg); and m4 by 29% (from 220 to 285 fmol/mg). In contrast, a 22% decrease in the density of m2 receptors was found (from 220 to 173 fmol/mg). Detectable levels of m5 receptors were low in the hippocampus (approximately 1% of total receptors), and reliable measurements were not obtained. The directions of these changes are likely to be related to the pre- or postsynaptic localization of these receptor subtypes.
Wall
S J
SJ
Department of Pharmacology, Georgetown University School of Medicine, Washington, District of Columbia 20007.
Wolfe
B B
BB
Kromer
L F
LF
D000818:Animals; D001665:Binding Sites; D002794:Choline / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003714:Denervation; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007163:Immunosorbent Techniques; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013396:Suction
D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002795:Choline O-Acetyltransferase; D002794:Choline