Pilocarpine-induced Salivation and Thirst in Conscious Rats

Abstract

The muscarinic receptor agonist pilocarpine is widely used as a sialogogue. It has been well-established that it also induces water intake in animals. However, the mechanisms underlying the relationships between these events are unknown. To address this problem, we examined water intake and parotid salivary secretion in conscious rats. Intraperitoneally injected pilocarpine increased both water intake and salivary secretion. Intracerebroventricularly injected pilocarpine also induced water intake, but not salivary secretion. Intracerebroventricularly applied atropine, a muscarinic receptor antagonist, suppressed the water intake produced by pilocarpine applied intraperitoneally and intracerebroventricularly. However, it did not affect the salivary secretion induced by pilocarpine applied peripherally. We conclude that peripherally applied pilocarpine affects the parotid glands and the thirst center in the central nervous system, while it may induce salivary secretion mainly via peripheral responses, but water intake mainly via the central nervous system.

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

“…Similar to pirenzepine, small doses of 4‐DAMP may block M 1 and/or M 3 receptors located periventricularly that are involved in the dipsogenic response and high doses are needed to block M 1 and/or M 3 receptors involved in pilocarpine‐induced salivation and pressor responses that are located far from the ventricles. A previous study ( Sato et al ., 2006 ) also showed that a small dose of i.c.v. atropine is effective at blocking i.p.…”

“…However, pirenzepine reduced pilocarpine‐induced pressor response only at the dose of 100 nmol, suggesting that central M 1 receptors activated by peripheral pilocarpine to produce dipsogenic responses are not the same as those involved in pressor responses and that they may be located in different central areas. Small doses of pirenzepine may block M 1 receptors localized more periventricularly or more specifically in circumventricular organs, such as the subfornical organ, an area suggested to be activated by pilocarpine to induce water intake in a previous study ( Sato et al ., 2006 ). High doses of pirenzepine are needed to reach areas that are not periventricular, that is, areas that are deeper in the central neural parenchyma and that are activated by pilocarpine to produce pressor responses.…”

“…It is well known that the activation of M 3 receptors directly in salivary glands produces salivation ( Iwabuchi et al ., 1994 ; Nakamura et al ., 2004 ; Sato et al ., 2006 , Proctor, 2006 ; Tobin et al ., 2006 ). However, pilocarpine administered systemically may cross the blood–brain barrier ( Freedman et al ., 1989 ) and, acting centrally, facilitate salivation as suggested by the reduction of i.p.…”

“…pilocarpine is reduced by forebrain lesions in the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V) region, lateral hypothalamus or medial preoptic area ( Renzi et al ., 1993 , 2002 ; Lopes de Almeida et al ., 2006 ). In spite of some discrepancies ( Sato et al ., 2006 ), the nonspecific ACh receptor antagonist atropine methyl bromide injected intracerebroventricularly at doses that act only centrally also reduces i.p. pilocarpine‐induced salivation ( Takakura et al ., 2003 ).…”

Thirst sensation and oral dryness following alcohol intake

“…To induce this thirst sensation, it is important to activate neurons in the circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO), and the hypothalamus, which are referred to as the dipsogenic center. Oral dryness, which comprises a feeling of dryness in the oral cavity, is produced by a decrease in salivary secretion [3], [4], [5] and is distinguished from thirst sensation [6], [7], [8], [9]. In the present review, thirst sensation and oral dryness after alcohol drinking or administration are differentiated.…”