Concentrations Of Arecoline Research Articles

Betel-nut chewing and asthma

Two Asian patients admitted to hospital with acute severe asthma had been chewing betel nut immediately before the attacks. Arecoline, a cholinergic alkaloid, is a major constituent of Areca catechu (betel) nut and causes the euphoric effects. We sought an association between betel-nut chewing and bronchoconstriction in asthmatic patients. In vitro, arecoline caused dose-related contraction of human bronchial smooth-muscle strips, with one-tenth the potency of methacholine. In a double-blind challenge study, inhalation of arecoline caused bronchoconstriction in six of seven asthmatic patients and one of six healthy subjects; methacholine caused bronchoconstriction in all the asthmatic patients and in five controls. The geometric mean concentrations of arecoline and methacholine that caused 20% falls in the forced expiratory volume in 1 s (PC 20 FEV 1) in the asthmatic subjects were 5·2 mg/ml and 1·6 mg/ml, respectively. We then studied four Bengali asthmatic patients, regular users of betel nut, during a betel-nut challenge. Three showed no adverse effects, but one showed a 30% fall in FEV 1 by 150 min after chewing; the effect was reproducible. In the UK, the rate of hospital admission for acute asthma is higher among Asians than among other groups in the population; betel-nut chewing may be one of several factors that affect asthma control and severity of attacks. Lancet 1992; 339: 1134-36.

Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Arecoline, an active alkaloid of Areca catechu L., and sodium nitrite, a food additive, are highly cytotoxic and cytostatic on the Hep 2 cell line when administered in an acidic environment (pH 4.2) in the presence of S-9 mixture. Hep 2 cells (10(6)) were treated with either 0.145, 0.725 or 1.449 mM sodium nitrite or 0.042, 0.085 or 0.339 mM arecoline or sodium nitrite (0.145 mM) plus varied concentrations of arecoline (0.042, 0.085 or 0.339 mM). Their effects were additive in nature. Hep 2 cells exposed to this combination showed reduced cell survival, and lower rates of DNA and protein syntheses. Involvement of N-nitroso derivatives of arecoline is suggested to explain the results. On the basis of these studies, we speculate that N-nitroso compounds derived from arecoline can (weakly) interact with DNA.

Influence of Arecoline on Immune System: II. Suppression of Thymus-Dependent Immune Responses and Parameter of Non-specific Resistance After Short-Term Exposure

Arecoline, a major alkaloid of arecanut was screened to explore its modulatory influence on cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at subtoxic concentrations of arecoline. Delayed type hypersensitivity (DTH) reactions to sheep red blood cells (SRBC) were evaluated in male mice. When treated subcutaneously with 20 mg/kg bw (1/5 of LD50) dose of arecoline for 1, 2 or 3 weeks, the DTH reactions were significantly suppressed. At arecoline concentration of 10 mg/kg bw, there was a moderate reduction in DTH response, while no appreciable change was observed at a dosage of 5 mg/kg bw. The effects were not dependent on the duration of treatment. In contrast, treating with arecoline continuously for 4 days following SRBC immunization showed significant suppression in DTH reactions at both 10 and 20 mg/kg bw doses. When treated after 12 h following immunization with 20 mg/kg bw arecoline, significant reduction in DTH reactions were seen. While moderate reduction in response was observed with arecoline dosage of 10 mg/kg bw, there was no alteration in response at the dose level of 5mg/kg bw. Recovery experiments in mice revealed that arecoline mediated effects are of a reversible nature. Arecoline treatment did not appreciably alter the host resistance to endotoxin shock. In vitro experiments revealed both dose-dependent and time-dependent cytotoxic effects of arecoline when spleen cells were incubated with varying concentrations of arecoline. Concomitant exposure of arecoline at concentrations of 10(-6) - 10(-4) M with con A, markedly suppressed both 3H-thymidine incorporation and interleukin-2 production of splenic cells. In contrast, concomitant exposure of arecoline with IL-2 did not alter 3H-thymidine incorporation in the IL-2 dependent cytolytic T-lymphocyte line (CTLL), except at the concentration of 10(-4) M arecoline. From these studies it is concluded that the dose-dependent suppressive effects of arecoline on DTH response to SRBC and on certain in vitro lymphocyte functions are more clear than the host resistance to endotoxin shock.

Pharmacological properties of presynaptic muscarinic receptors in the sixth abdominal ganglion of the cockroach, Periplaneta americana L.

AbstractThe effects of muscarinic agonists on acetylcholine (ACh) release in the cercal‐afferent giant‐interneuron synapses of the cockroach have been studied using the single‐fibre oil‐gap method. Decrease in amplitude of the cEPSP was induced by pressure ejection of arecoline (ARE), carbachol (CCh) and oxotremorine free base (OXO) within the sixth abdominal (A6) ganglion. This depressive effect was dose‐dependent without any effect at the post‐synaptic site in the range of concentrations used. The concentration for 50% of cEPSP inhibition of the most commonly used muscarinic agonists was determined. The rank order of potencies was: ARE > CCh > OXO > McN‐A‐343 > bethanechol (BET). Plateau levels of 56%, 54% and 68% were reached when increasing the concentration of ARE, CCh and OXO respectively. McN‐A‐343 and BET had an inhibitory effect on ACh release but higher doses also acted at the postsynaptic level. Furthermore, muscarinic agonists were able to evoke uIPSP and a smaller inhibitory effect of ARE and OXO was observed in presence of picrotoxin.It is concluded that the ACh release in the cockroach A6 ganglion is modulated by presynaptic muscarinic receptors which are possible target sites for insecticides. The presence of putative muscarinic receptors on inhibitory GABAergic interneurons, involved in pre‐ and postsynaptic inhibition is suspected.

Regional brain metabolic responsivity to the muscarinic cholinergic agonist arecoline is similar in young and aged Fischer-344 rats

In order to determine whether a functional deficit in brain cholinoception accompanies the reported loss of muscarinic receptors with age, local cerebral glucose utilization (LCGU) was measured in awake 3- and 24-month-old rats after the administration of the muscarinic cholinergic agonist arecoline. Awake, male Fischer-344 rats received isotonic saline or arecoline (0.05–50 mg/kg), i.p., and LCGU was measured in 95 regions with the [ 14C]2-deoxy- d-glucose technique. Plasma and brain pharmacokinetics of arecoline in rats of both ages were measured in a separate experiment and were found not to differ between the two age groups. Peak cerebral cortex arecoline concentrations, at 3 min after the administration of 5 mg/kg, i.p., were 1558 ± 588and1830 ± 317ng/g in 3- and 24-month-old rats, respectively. LCGU effects were dose-dependent, with fewer regions activated by smaller doses. In 24-month-old rats, arecoline in one or more doses elevated LCGU significantly in 94% of the regions examined; no declines in LCGU were found. Increases in whole brain glucose utilization produced by all doses of arecoline, compared to control values, were similar in 3- and 24-month-old rats. After one or more doses, the rise in LCGU in 24-month-old animals, compared to that in 3-month rats, was not significantly different in 75 brain regions, greater in 13 and smaller in 7. These findings demonstrate that the functional responsivity of brain regions to a cholinergic agonist is, for the most part, age-invariant in the rat, implying that the function of muscarinic receptor and postreceptor mechanisms remains intact despite reported age-related losses of muscarinic receptors.

Hypothalamic superfusion with muscarinic drugs: their effects on pressor responses to hypothalamic stimulation.

The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused with artificial cerebrospinal fluid through a push-pull cannula and electrically stimulated with the noninsulated tip of the cannula. The effects of muscarinic drugs on the pressor response to stimulation of the hypothalamus were investigated. Superfusion with muscarine, oxotremorine or N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) decreased the pressor responses to hypothalamic stimulation. Superfusion with methylatropine did not influence the pressor responses to hypothalamic stimulation; however, superfusion with methylatropine 60 min prior to and during superfusion with the muscarinic drugs abolished the inhibitory effects of muscarine and oxotremorine and temporarily reversed that of AHR 602 on the pressor responses. Superfusion of the posterior hypothalamus with arecoline enhanced the rise of blood pressure elicited by hypothalamic stimulation. When the hypothalamus was superfused with hexamethonium 60 min prior to and during superfusion with arecoline, arecoline reduced the pressor responses to electrical stimulation of the hypothalamus. Superfusion with methylatropine prior to and together with an ineffective concentration of arecoline increased the rise of blood pressure elicited by hypothalamic stimulation. From the drugs studied here only oxotremorine caused a fall of the "resting" arterial blood pressure; it was abolished by the intravenous injection of methylatropine. From these results it was concluded that superfusion of the posterior hypothalamus with muscarinic drugs impairs the pressor responses to hypothalamic stimulation. Drugs possessing both nicotinic and muscarinic properties either enhance or diminish the pressor responses according to their relative potencies on the two types of receptor.