Ontogeny of cortical muscarinic receptor subtypes and muscarinic receptor-mediated responses in rat.

To determine the ontogenetic relationship of muscarinic receptor and effector systems in the central nervous system, the developmental time courses for binding sites with high (M1) and low (M2) affinity for pirenzepine as well as muscarinic receptor-mediated stimulation of phosphoinositide breakdown and inhibition of cyclic AMP accumulation were examined in rat cortex. M1 sites were 30% of adult levels at 1 week, 70% at 2 weeks, 90% at 3 weeks and equal to adult levels at 4 weeks postpartum. M2 sites, on the other hand, did not show a significant change between the ages of 1 and 6 weeks. Acetylcholine-stimulated phosphoinositide breakdown was detected at all ages tested (1, 2, 3, 4 and 6 weeks). The percentage of conversion of [3H] phosphoinositides to [3H]inositol phosphates, stimulated by 1 mM acetylcholine, increased with age until 3 weeks after birth and then decreased slightly at ages 4 and 6 weeks. Carbachol inhibition of [3H]cyclic AMP accumulation, on the other hand, was undetectable in tissues from 1- and 2-week-old rats, whereas in tissues from 3- and 4-week-old rats, the responses were at 6-week level. Thus, for carbachol inhibition of cyclic AMP accumulation, a time in development existed (2 weeks after birth) at which receptors appeared to be present but response to stimulation was absent. To examine indirectly the coupling of binding sites to second messenger systems via guanine nucleotide-binding regulatory proteins, the density of binding sites for the muscarinic receptor agonist, [3H]oxotremorine-M, was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

[3H]SCH 23390 labels both dopamine-1 and 5-hydroxytryptamine1c receptors in the choroid plexus.

[3H]SCH 23390 has been used to label the D-1 subtype of dopamine receptors. Quantitative autoradiographic studies with [3H]SCH 23390 have revealed high levels of binding in many regions of rat brain including the caudate-putamen, nucleus accumbens, substantia nigra and choroid plexus. The selectivity of the binding of [3H]SCH 23390 was characterized further in studies using homogenates of canine choroid plexus. Scatchard analysis of the binding of increasing concentrations of [3H]SCH 23390 resulted in a curvilinear plot when (+)-butaclamol was used to define specific binding. Nonlinear regression analysis of untransformed data was consistent with the presence of two distinct classes of binding sites. The high-affinity site (Kd, 0.4 nM) was present at low density (maximum binding sites, 30 fmol/mg of protein) and had the pharmacological properties expected of a D-1 receptor. The low-affinity site (Kd, 24 nM) was present at a much greater density (maximum binding sites, 350 fmol/mg of protein) and had the pharmacological properties expected of a 5-hydroxytryptamine1c receptor. Quantitative autoradiographic studies of the binding of [3H]SCH 23390 to sections of rat brain also suggested that 5-hydroxytroptamine1c receptors in the choroid plexus are labeled by [3H]SCH 23390. It is possible that [3H]SCH 23390 labels 5-hydroxytryptamine1c receptors in other brain regions as well.

Rotational behavior following cholinergic stimulation of the superior colliculus in rats.

Rate which received microinjections of carbachol into the superior colliculus exhibited pronounced dose-dependent rotational behavior contralateral to the site of injection (Experiment 1). Wet dog shakes were also observed in some animals. Similar injections in the midbrain reticular formation produced immobility with slight contralateral flexion of the neck. Convulsions were observed in some rats after injections into either anatomical location. In Experiment 2, circling induced by carbachol in the superior colliculus was blocked by prior injection of either the muscarinic receptor antagonist scopolamine or the nicotinic receptor antagonist mecamylamine, suggesting that both nicotinic and muscarinic receptors are involved in the effect. In Experiment 3 contralateral rotational behavior was induced by intracollicular microinjections of the combination of acetylcholine chloride and physostigmine. The results suggest that collicular mediation of contralateral rotational behavior, and perhaps orientation, might involve cholinergic receptors.