Muscarinic receptor characteristics and regulation in rat cerebral cortex: changes during development, aging and the oestrous cycle.
The effects of postnatal development, aging and the oestrous cycle on muscarinic acetylcholine receptor (mAChR) properties were examined in in vitro living slices of rat neocortex. Using the hydrophilic antagonist ([3H]NMS) to label cell surface mAChRs, an increase in both Bmax and Kd was found during the first postnatal weeks. These values peaked at between 20-40 days postnatally and then declined to adult levels. After 3 months of age, a steady decline in receptor number started: it was 10.1% lower at 10 months and 38.7% lower at 17 months of age. In contrast, Kd values increased, being 31.7 and 20% higher respectively at these ages. Carbachol-induced (4 h at 37 degrees C) down-regulation of receptor number was approximately 22.2% in newborn and 26.1% in adult (3-month-old) rats, but only 16.3% at 20-40 days of age. The degree of carbachol-induced down-regulation of mAChR was not affected in the older animals. Veratridine, which increases neural activity, also induced a significant reduction in [3H]NMS binding sites of 11.4% in rats aged 0-20 days and 22.4% in 3-month-old rats, but at 20-40 and 40-60 days of age no significant down-regulation of receptor number was observed. Furthermore, down-regulation was absent in the 10-month-old rats as well. Since a great variation in Bmax and Kd values was seen in 3-month-old females but not in male rats, we investigated mAChR characteristics during the oestrous cycle of female rats. In pro-oestrus, mACh receptor number was increased and affinity decreased in comparison with di-oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)
van Huizen
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Organon International BV, Department of Neuropharmacology, Oss, The Netherlands.
March
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Cynader
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Shaw
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation; D004971:Estrus / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D019832:N-Methylscopolamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D019832:N-Methylscopolamine