Barry B. Wolfe

Selective increases in the density of cerebellarβ1-adrenergic receptors

Destruction of noradrenergic neurons by 6-hydroxydopamine or chronic blockade of β-adrenergic receptors with propranolol increased the density ofβ1-adrenergic receptors two-fold in rat cerebellum but had no effect on the density ofβ2-adrenergic receptors. The results suggest that even thoughβ1 receptors comprise only 5–10% of the total number of β-adrenergic receptors in the cerebellum they are the receptors specifically innervated by noradrenergic neurons and they may thus be the physiologically important receptors.

Selective changes in the density of ß1-adrenergic receptors in rat striatum following chronic drug treatment and adrenalectomy

The corpus striatum has a high density of beta-adrenergic receptors though it appears to contain low levels of beta-hydroxylated catecholamines. In an attempt to determine whether these receptors normally receive an endogenous input, the densities of beta 1 and beta 2-adrenergic receptors in rat caudate have been measured following adrenalectomy and after various pharmacological manipulations. Chronic administration of either pargyline, an inhibitor of monoamine oxidase activity, or desmethylimipramine, an inhibitor of norepinephrine uptake, resulted in a 20-25% decrease in the density of beta 1-adrenergic receptors while either adrenalectomy or the chronic administration of the non-selective beta-adrenergic receptor antagonist propranolol resulted in small but significant increases in the density of beta 1-receptors. These treatments did not lead to significant changes in the density of beta 2-receptors. It thus appears that the density of beta 1-receptors in the caudate is normally affected by changing levels of endogenous catecholamines.

Effects of hypoxia on atrial muscarinic cholinergic receptors and cardiac parasympathetic responsiveness

Chronic exposure of rats to hypoxia resulted in a lower resting heart rate and a supranormal increase in heart rate in response to parasympathetic blockade by atropine. The density of muscarinic cholinergic receptors labeled by the antagonist [3H]quinuclidinyl benzilate was elevated significantly in the atria of animals kept hypoxic for 2-4 weeks. Chronic hypoxia did not change the affinity of the receptor for [3H]quinuclidinyl benzilate, the weight of the atria, or the amount of protein per atrial pair. Thus, the decrease in resting heart rate may be explained by the increase in the density of atrial muscarinic cholinergic receptors.

[3H]Acetylcholine Binding to Nicotinic Cholinergic Receptors in Brain: Localization and Regulation Visualized by Autoradiography

[3H]Acetylcholine ([3H]ACh) labels nicotinic cholinergic receptors of high affinity in brain homogenates (1). The distribution of these sites can be studied in greater detail using autoradiographic techniques. In a recent autoradiographic study, a qualitative comparison was made of [3H]ACh and [3H]nicotine binding to nicotinic cholinergic receptors in rat brain sections (2). In the present study, autoradiography was used to determine the relative distribution of [3H]ACh binding sites throughout several levels of rat brain. Brain sections (24 ym) were thaw-mounted onto subbed slides, assayed for [3H]ACh binding, and exposed to tritiunv-sensitive film as previously described (2,3). Optical density measurements were made of specific brain regions relative to areas of white matter in the same slice. There was a seven-fold difference between areas with the highest and lowest levels of [3H]ACh binding. The greatest binding occurred in areas such as the interpeduncular nucleus, several thalamic nuclei, and medial habenula. Areas with moderate levels of binding included the superior colliculus, retrosplenial cortex, substantia nigra pars compacta, and caudate nucleus, while [3H]ACh binding was virtually absent in areas such as the inferior colliculus, hippocampus (stratum oriens), and entorhinal cortex. In previous studies using brain homogenates, we have observed that repeated exposure to the cholinesterase inhibitor OFP leads to a ‘down-regulation’ of [3H]ACh binding sites while repeated exposure to nicotine leads to an ‘up-regulation’ of these binding sites in brain areas such as the thalamus, cortex, caudate, and hypothalamus (4,5).