Central muscarinic receptor subtypes involved in pilocarpine‐induced salivation, hypertension and water intake

Abstract

Background and purpose: Recent evidence has suggested that pilocarpine (ACh receptor agonist) injected peripherally may act centrally producing salivation and hypertension. In this study, we investigated the effects of specific M 1 (pirenzepine), M 2 /M 4 (methoctramine), M 1 /M 3 (4-DAMP) and M 4 (tropicamide) muscarinic receptor subtype antagonists injected into the lateral cerebral ventricle (LV) on salivation, water intake and pressor responses to peripheral pilocarpine. Experimental approach: Male Holtzman rats with stainless steel cannulae implanted in the LV were used. Salivation was measured in rats anaesthetized with ketamine (100 mg per kg body weight) and arterial pressure was recorded in unanaesthetized rats. Key results: Salivation induced by i.p. pilocarpine (4 mmol per kg body weight) was reduced only by 4-DAMP (25-250 nmol) injected into the LV, not by pirenzepine, methoctramine or tropicamide at the dose of 500 nmol. Pirenzepine (0.1 and 1 nmol) and 4-DAMP (5 and 10 nmol) injected into the LV reduced i.p. pilocarpine-induced water intake, whereas metoctramine (50 nmol) produced nonspecific effects on ingestive behaviours. Injection of pirenzepine (100 nmol) or 4-DAMP (25 and 50 nmol) into the LV reduced i.v. pilocarpine-induced pressor responses. Tropicamide (500 nmol) injected into the LV had no effect on pilocarpine-induced salivation, pressor responses or water intake. Conclusions and implications:The results suggest that central M 3 receptors are involved in peripheral pilocarpine-induced salivation and M 1 receptors in water intake and pressor responses. The involvement of M 3 receptors in water intake and pressor responses is not clear because 4-DAMP blocks both M 1 and M 3 receptors.

Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography

“…Recently, pharmacological studies have shown that forebrain lesions or intraventricular injection of atropine reduced pilocarpine-induced salivation, indicating central mechanism of salivary secretion (Takakakura et al 2003;Lopes de Almeida et al 2006). In addition Borella et al (2008) have demonstrated central M 3 receptors to be involved in pilocalpine-induced salivation. Therefore, the extensive distribution of oxybutynin in the CNS might lead to peripheral adverse effects such as dry mouth.…”

Sodium intake combining cholinergic activation and noradrenaline into the lateral parabrachial nucleus

“…water intake induced by pilocarpine i.p. depends on activation of central muscarinic receptors (Borella et al, 2008). A difference is that rats treated with carbachol i.c.v.…”

“…The doses of the drugs used were based on previous studies that injected these drugs central or peripherally (Camargo et al, 1984(Camargo et al, , 2009Menani et al, , 2000Andrade et al, 2004;Borella et al, 2008).…”

“…Inhibitory signals for sodium and water intake arise from arterial baroreceptors or cardiopulmonary receptors that are activated by increases in arterial pressure or body fluid volume (Johnson and Thunhorst, 1997;De Gobbi et al, 2008). Therefore, a reason for the absence of hypertonic NaCl intake in rats treated with central cholinergic agonists might be the inhibitory signals produced in response to the increases in arterial pressure caused by these treatments (Trendelenburg, 1961;Hoffman et al, 1977;Imai et al, 1989;Thunhorst and Johnson, 1994;Johnson and Thunhorst, 1997;Takakura et al, 2003Takakura et al, , 2005Takakura et al, , 2011Borella et al, 2008). Reducing the action of the inhibitory signals with bilateral injections of methysergide (serotonergic receptor antagonist) into the LPBN results in significant ingestion of hypertonic NaCl in rats treated with the cholinergic agonist carbachol intracerebroventricularly (i.c.v.)…”

Tramadol-induced oral dryness and pilocarpine treatment: Effects on total protein and IgA

“…Besides activation of the glandular muscarinic receptors, pilocarpine activates muscarinic receptors in the central nervous system. 26 The central activation could of course lead to stimulation of the salivary glands from both divisions of the autonomic nervous system. By this it follows that the composition of pilocarpine-induced saliva does not exclusively reflects a salivary response of the parasympathetic nervous system.…”