Arecoline

About: Arecoline is a research topic. Over the lifetime, 744 publications have been published within this topic receiving 16015 citations. The topic is also known as: methylarecaiden & methylarecaidin.

Muscarinic Cholinergic Modulation of Prepulse Inhibition of the Acoustic Startle Reflex

Abstract: The purpose of the present study was to determine the effects of muscarinic cholinergic receptor antagonists and agonists on prepulse inhibition (PPI) of the acoustic startle reflex in rats. The muscarinic receptor antagonist scopolamine (0.03–1.0 mg/kg) produced a significant dose-dependent decrease in PPI without affecting startle amplitude. In contrast, N -methyl scopolamine, the quaternary analog of scopolamine, had no effect on PPI, indicating that scopolamine disrupted PPI through a central cholinergic mechanism. Two other muscarinic receptor antagonists, trihexyphenidyl (0.3–10 mg/kg) and benztropine (0.03–10 mg/kg), produced significant decreases in PPI similar to scopolamine. On the other hand, the muscarinic receptor antagonists dicyclomine (0.03–10 mg/kg) and biperiden (0.03–10 mg/kg) had no effect on PPI but significantly decreased startle amplitude. Mecamylamine (0.1–10 mg/kg), a nicotinic receptor antagonist, also had no effect on PPI. Administered alone, the muscarinic receptor agonists pilocarpine (0.03–10 mg/kg), oxotremorine (0.01–0.3 mg/kg), RS-86 (0.1–3.0 mg/kg), and arecoline (0.3–10 mg/kg), as well as the cholinesterase inhibitors physostigmine (0.01–0.3 mg/kg) and tacrine (0.03–10 mg/kg), had no effect on PPI, but each produced significant decreases in startle amplitude at the highest doses tested. In addition, the disruption of PPI by scopolamine was reversed in a dose-dependent manner by the muscarinic receptor agonist oxotremorine. The present findings demonstrate that the muscarinic cholinergic system plays an important role in the normal mechanisms of PPI.

Activation of TGF-β Pathway by Areca Nut Constituents: A Possible Cause of Oral Submucous Fibrosis

Abstract: Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as an important etiological factor for disease manifestation. Activation of transforming growth factor-β signaling has been postulated as the main causative event for increased collagen production in OSF. Oral epithelium plays important roles in OSF, and arecoline has been shown to induce TGF-β in epithelial cells. In an attempt to understand the role of areca nut constituents in the manifestation of OSF, we studied the global gene expression profile in epithelial cells (HaCaT) following treatment with areca nut water extract or TGF-β. Interestingly, 64% of the differentially regulated genes by areca nut water extract matches with the TGF-β induced gene expression profile. Out of these, expression of 57% of genes was compromised in the presence of ALK5 (TβRI) inhibitor and 7% were independently induced by areca nut, highlighting the importance of TGF-β in areca nut actions. Areca nut water extract treatment induced p-SMAD2 and TGF-β downstream targets in HaCaT cells but not in human gingival fibroblast cells (hGF), suggesting epithelial cells could be the source of TGF-β in promoting OSF. Water extract of areca nut consists of polyphenols and alkaloids. Both polyphenol and alkaloid fractions of areca nut were able to induce TGF-β signaling and its downstream targets. Also, SMAD-2 was phosphorylated following treatment of HaCaT cells by Catechin, Tannin and alkaloids namely Arecoline, Arecaidine and Guvacine. Moreover, both polyphenols and alkaloids induced TGF-β2 and THBS1 (activator of latent TGF-β) in HaCaT cells suggesting areca nut mediated activation of p-SMAD2 involves up-regulation and activation of TGF-β. These data suggest a major causative role for TGF-β that is induced by areca nut in OSF progression.

The cholinergic rapid eye movement induction test with arecoline in depression.

Abstract: The cholinergic rapid eye movement (REM) induction test using arecoline hydrobromide, a cholinergic muscarinic receptor agonist, was studied in patients with affective disorder and in normal controls to determine whether or not depression is associated with enhanced induction of REM sleep by muscarinic agonists. Arecoline induced REM sleep in a dose-dependent fashion in both patients and controls compared with placebo infusions. Compared with normal controls, patients entered REM sleep significantly more rapidly following intravenous administration of 1.0 mg of arecoline hydrobromide than they did following administration of 0.5 mg of arecoline hydrobromide or placebo. These results, as well as those of previous studies, support the hypothesis that patients with affective disorder show a functional supersensitive induction of REM sleep in response to muscarinic receptor agonists and may be consistent with the hypothesis that functional muscarinic receptor "up regulation" is associated with depression.