Blockade Of Central Cholinergic Receptors Research Articles

Central muscarinic receptors signal pilocarpine-induced salivation.

Although cholinergic agonists such as pilocarpine injected peripherally can act directly on salivary glands to induce salivation, it is possible that their action in the brain may contribute to salivation. To investigate if the action in the brain is important to salivation, we injected pilocarpine intraperitoneally after blockade of central cholinergic receptors with atropine methyl bromide (atropine-mb). In male Holtzman rats with stainless steel cannulas implanted into the lateral ventricle and anesthetized with ketamine, atropine-mb (8 and 16 nmol) intracerebroventricularly reduced the salivation induced by pilocarpine (4 micro mol/kg) intraperitoneally (133 + 42 and 108 + 22 mg/7 min, respectively, vs. saline, 463 + 26 mg/7 min), but did not modify peripheral cardiovascular responses to intravenous acetylcholine. Similar doses of atropine-mb intraperitoneally also reduced pilocarpine-induced salivation. Therefore, systemically injected pilocarpine also enters the brain and acts on central muscarinic receptors, activating autonomic efferent fibers to induce salivation.

Autonomic neural control mechanisms of substrate and hormonal responses to acute hypoglycaemia in man.

The contributions of adrenergic and cholinergic mechanisms to recovery from acute hypoglycaemia induced by insulin (0.15 units/kg i.v.) were examined in eleven normal subjects, six subjects with a pre-ganglionic sympathectomy (adrenergic denervation) and six sympathectomized subjects given atropine (combined adrenergic denervation and cholinergic blockade). Blood glucose recovery was impaired only in the sympathectomized subjects given atropine. The blood lactate response was reduced and the rise in free fatty acids was delayed in both groups of sympathectomized subjects, in whom the normal rises of plasma cyclic AMP and noradrenaline were absent. The plasma pancreatic glucagon response was appropriate to the prevailing blood glucose concentrations in all three groups. The cortisol response was impaired and the pattern of ACTH secretion was abnormal in sympathectomized subjects given atropine. Growth hormone levels were higher in both sympathectomized groups. Blood glucose homeostasis was impaired during combined adrenergic denervation and cholinergic blockade. Glucagon secretion was activated independently of vagal control. In the sympathectomized group given atropine, the rise in plasma cortisol was blunted despite a greater degree of hypoglycaemia. A blockade of central cholinergic receptors producing impaired activation of ACTH secretion at hypothalamic level may explain, at least in part, this delayed restoration of normoglycaemia.

Central cholinergic receptor supersensitivity after long-term atropine administration.

Rats were treated with a single dose of atropine (AT) at 5 mg/kg, or every day for 14 or 31 days with the same dose of AT, 3 h after the single dose and 24 h after the last dose of chronically administered AT, 10 micrograms of ACh was injected intracerebroventricularly, and two tests were used to examine the behavior of the animals. The tremorigenic effect of oxotremorine was also measured in mice treated with 10 mg/kg of AT for 1 month. It was shown that a single dose of AT antagonized ACh-induced behavior. The long-term treatment with AT enhanced the depressive-behavior of ACh in rats and the tremorigenic effect of oxotremorine in mice. The results suggest that long-term blockade of central cholinergic receptors induces their hypersensitivity.