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

Department of Physiology and Pathology, School of Dentistry, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
British Journal of Pharmacology (Impact Factor: 4.84). 10/2008; 155(8):1256-63. DOI: 10.1038/bjp.2008.355
Source: PubMed


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.
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.
Salivation induced by i.p. pilocarpine (4 micromol 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.
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.

Download full-text


Available from: Débora S A Colombari, Jul 07, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The current study was conducted to evaluate, by the noninvasive positron emission tomography (PET), the binding of antimuscarinic agents used to treat overactive bladder (OAB) to muscarinic receptors in rat brain. Muscarinic receptor occupancy in the rat brain after the intravenous (i.v.) injection of oxybutynin, darifenacin and imidafenacin was evaluated by using a small animal PET system, and compared with the results by ex vivo autoradiographic and ex vivo radioligand binding experiments. In PET study, the i.v. injection of oxybutynin but not darifenacin or imidafenacin at pharmacological doses decreased significantly binding potential (BP) of (+)N-[(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB) in the rat cerebral cortex and corpus striatum in a dose-dependent manner. Similarly, in the in vivo autoradiographic experiment, oxybutynin dose-dependently reduced binding of [(11)C](+)3-MPB in the brain, whereas darifenacin and imidafenacin did not. Following the i.v. injection of oxybutynin, darifenacin and imidafenacin, there was a similar degree of binding to muscarinic receptors in the bladder as demonstrated by a significant increase in apparent dissociation constant (K(d)) values for specific [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS) binding. Significant binding of muscarinic receptors in the brain was observed after the injection of oxybutynin but not darifenacin or imidafenacin. Oxybutynin but not darifenacin or imidafenacin has potential side effects on the central nervous system (CNS) in patients with OAB. The results reveal the noninvasive characterization of brain receptor occupancy by PET to be a powerful tool for precise evaluation of adverse CNS effects of antimuscarinic agents in pre-clinical and clinical evaluations.
    Full-text · Article · Jul 2010 · Life sciences

  • No preview · Article · Jan 1995
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A novel method for retrieving images based on relevance feedback and clustering has been developed. That is, by clustering sets of retrieved data, a user can select some good answers from them by considering the difference between the feature data of the selected images and the feature data of images placed in their neighborhood. This difference information improves previous queries since the user must have found some important difference between their-selected image and similar neighboring images. An image-retrieval system based on a relevance feedback by difference amplification is set up and shown to be more effective than conventional methods.
    Full-text · Conference Paper · Aug 2003
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.