Activation of α2-adrenoceptors in the lateral hypothalamus reduces pilocarpine-induced salivation in rats (original) (raw)
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Autonomic Neuroscience, 2004
We determined the effects of moxonidine and rilmenidine 20 nmol (a 2 -adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250 -300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg À 1 b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg À 1 ) injected i.p. (12 F 3 mg min À 1 ) vs. control (99 F 9 mg min À 1 ). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20 F 5 mg min À 1 ) vs. control (94 F 7 mg min À 1 ). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60 F 8 and 95 F 10 mg min À 1 , respectively). Yohimbine 40 nmol (a 2 -adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70 F 6 and 24 F 6 mg min À 1 , respectively). Injection of these a 2 -adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of a 2 -adrenergic and imidazoline agonists' agents inhibit pilocarpineinduced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that a 2 -adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially. These receptors of the medial septal area have an inhibitory mechanism on salivary secretion. D
Moxonidine reduces pilocarpine-induced salivation in rats
Autonomic Neuroscience-basic & Clinical, 2001
Cholinergic agonists activate salivation and the a -adrenergic and imidazoline receptor agonists induce opposite effects. In the present 2 Ž . Ž . Ž study, we investigated the effects of intracerebroventricular i.c.v. or intraperitoneal i.p. injection of moxonidine an a -adrenergic and 2 2
Inhibition of pilocarpine-induced salivation in rats by central noradrenaline
Archives of oral …, 2002
Peripheral treatment with cholinergic or adrenergic agonists results in salivation and the possibility of synergy between cholinergic and adrenergic efferent mechanisms in the control of salivation has been proposed. Central injections of the cholinergic agonist pilocarpine also induce salivation, while the effects of central injections of noradrenaline (norepinephrine) are not known. Here (a) the effects of intracerebroventricular (icv) injection of noradrenaline on the salivation induced by icv or intraperitoneal (i.p.) injection of pilocarpine and (b) the receptors involved in the effects of central noradrenaline on pilocarpine-induced salivation were investigated. Male Holtzman rats with a stainless-steel guide cannula implanted into the lateral ventricle were used. Rats were anaesthetized with tribromoethanol (200 mg/kg body weight) and saliva was collected on small, preweighed cotton balls inserted into the animal’s mouth. Noradrenaline (40, 80 and 160 nmol/1 μl) injected icv reduced the salivary secretion induced by pilocarpine (0.5 μmol/1 μl) injected icv. Noradrenaline (80 and 160 nmol/1 μl) injected icv also reduced the salivation induced by pilocarpine (4 μmol/kg) injected i.p. Previous treatment with the α2-adrenergic receptor antagonists RX 821002 (40, 80 and 160 nmol/1 μl) or yohimbine (160 and 320 nmol/1 μl) abolished the inhibitory effect produced by icv injection of noradrenaline on pilocarpine-induced salivation in rats. Prazosin (α1-adrenergic receptor antagonist) injected icv did not change the effect of noradrenaline on pilocarpine-induced salivation. Prior icv injection of only RX 821002 (80 or 160 nmol/1 μl) or yohimbine (320 nmol/1 μl) increased pilocarpine-induced salivation. The results show that (1) contrary to its peripheral effects, noradrenaline acting centrally inhibits cholinergic-induced salivation in rats; (2) central mechanisms involving α2-adrenergic receptors inhibit pilocarpine-induced salivation.
Central moxonidine on salivary gland blood flow and cardiovascular responses to pilocarpine
Brain research, 2003
Peripheral treatment with the cholinergic agonist pilocarpine induces intense salivation that is inhibited by central injections of the α2-adrenergic/imidazoline receptor agonist moxonidine. Salivary gland blood flow controlled by sympathetic and parasympathetic systems may affect salivation. We investigated the changes in mean arterial pressure (MAP) and in the vascular resistance in the submandibular/sublingual gland (SSG) artery, superior mesenteric (SM) artery and low abdominal aorta (hindlimb) in rats treated with intraperitoneal (i.p.) pilocarpine alone or combined with intracerebroventricular (i.c.v.) moxonidine. Male Holtzman rats with stainless steel cannula implanted into lateral ventricle (LV) and anesthetized with urethane were used. Pilocarpine (4 μmol/kg of body weight) i.p. reduced SSG vascular resistance (−50±13% vs. vehicle: 5±3%). Pilocarpine i.p. also increased mesenteric vascular resistance (15±5% vs. vehicle: 2±3%) and MAP (16±3 mmHg, vs. vehicle: 2±3 mmHg). Moxonidine (20 nmol) i.c.v. increased SSG vascular resistance (88±12% vs. vehicle: 7±4%). When injected 15 min following i.c.v. moxonidine, pilocarpine i.p. produced no change on SSG vascular resistance. Pilocarpine-induced pressor responses and increase in mesenteric vascular resistance were not modified by i.c.v. moxonidine. The treatments produced no change in heart rate (HR) and hindlimb vascular resistance. The results show that (1) i.p. pilocarpine increases mesenteric vascular resistance and MAP and reduces salivary gland vascular resistance and (2) central moxonidine increases salivary gland vascular resistance and impairs pilocarpine-induced salivary gland vasodilatation. Therefore, the increase in salivary gland vascular resistance may play a role in the anti-salivatory response to central moxonidine.
Life Sciences, 2002
Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 mg/ml) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 mg/ml), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 mg/ml) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of 0024-3205/02/$ -see front matter D 2002 Elsevier Science Inc. All rights reserved. PII: S 0 0 2 4 -3 2 0 5 ( 0 2 ) 0 1 5 3 1 -X (W.A. Saad).
Studies of muscarinic receptor subtypes in salivary gland function in anaesthetized rats
2002
The in vivo study aimed to examine whether muscarinic receptor subtypes other than muscarinic M 3 receptors exert exocrine functional roles in the rat salivary glands. The effects of pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were examined on secretion from the major salivary glands evoked by acetylcholine (0.001 -10 Amol kg À 1 i.v.) in pentobarbitoneanaesthetized rats. Observations were occasionally made on glandular blood flow. 4-DAMP (0.1 -100 nmol kg À 1 i.v.) markedly and equipotently inhibited the acetylcholine-evoked fluid responses in all glands. Pirenzepine (0.1 Amol kg À 1 i.v. -10 mmol kg À 1 i.v.) showed significantly lower inhibitory potency than 4-DAMP, most conspicuously in the parotid, while methoctramine (0.1 Amol kg À 1 i.v. -10 mmol kg À 1 i.v.) exerted an even lesser inhibitory effect. Also against acetylcholine-evoked blood flow increases, 4-DAMP showed a conspicuous potency. At 1 and 10 Amol kg À 1 i.v. of pirenzepine, the antagonist reduced the protein concentration in the submandibular saliva, but not in the parotid saliva. While 4-DAMP (1 and 10 nmol kg À 1 i.v.) significantly inhibited acetylcholine-evoked protein secretory responses in the submandibular glands, methoctramine (below 10 Amol kg À 1 i.v.) affected the responses in neither gland. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by N N -nitro-L-arginine methyl ester (L-NAME; 30 mg kg À 1 i.p.), while L-NAME had no or only minute effects on the parotid protein secretion. Thus, in addition to muscarinic M 3 receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular and sublingual glands. While these other receptors are muscarinic M 1 receptors in the sublingual gland, they may be a different subtype, possibly muscarinic M 5 receptors, in the submandibular gland. However, muscarinic M 1 receptors may induce indirect effects via nitric oxide in the submandibular gland. D
Comparison of the effects of pilocarpine and cevimeline on salivary flow
International Journal of Dental Hygiene, 2009
Objective: The aim of the present study was to compare the effect of low-dose pilocarpine and cevimeline as stimulants for salivary flow in healthy subjects. Methods: In this cross-over clinical trial with a 1-week washout period, 40 male volunteers were submitted to an oral dose of pilocarpine 1% (Salagen TM ) )60 lg kg )1 body-weight (Group 1) or Cevimeline (Evoxac TM ) )30 mg (Group 2). Saliva samples were collected and the salivary flow rate was measured (ml min )1 ) at baseline and 20, 40, 60, 80, 140 and 200 min after administration of drugs. In addition, salivary secretion was also measured under mechanical stimulation to observe salivary gland function. Results: The data were analyzed by Friedman and Wilcoxon signed-rank tests (significance level = 5%). Pilocarpine and cevimeline significantly increased salivary flow 140 min after intake. There was a significant higher secretion with cevimeline 140 and 200 min after administration. There were no differences seen among subjects in the salivary glands function by mechanical stimulation. Conclusion: Both drugs showed efficacy in increasing the salivary flow in healthy volunteers, but cevimeline was more effective than pilocarpine. Xerostomia is a symptom associated with quantitative and qualitative changes in the salivary flow, which are generally attributed to salivary hypofunction. Several factors can cause a decrease in the salivary flow. These include autoimmune exocrinopathies (Sjö gren's syndrome), anticholinergic effects of many drugs, tricyclic antidepressants, antihistaminic agents, antihypertensives and diuretics. Treatment of head and neck cancers with ionizing radiation, HIV infection, hepatitis C, Diabetes mellitus, hypertension, depression, aging, decrease of masticatory function, smoking, trauma, psychological and physiological changes can also negatively influence the salivary flow (4-9). A significant reduction in the salivary flow usually interferes in the quality of life and can cause oral dysfunction, dental destruction, atrophy and ulceration of mucosa and mucosal infection. It is important to recognize and treat salivary flow dysfunction. The treatment of choice is usually some kind of sialogogue, with pilocarpine or cevimeline being the most used (2, 9-11).