Showing papers on "Arecoline published in 1995"

The selective 5-HT3 receptor antagonist, WAY100289, enhances spatial memory in rats with ibotenate lesions of the forebrain cholinergic projection system.

Abstract: The effects of three doses (0.003, 0.03 and 1.0 mg/kg sc) of the 5-HT3 receptor antagonist, WAY 100289, on spatial learning and memory in the water maze were examined in rats before and after ibotenate lesions to the nucleus basalis and medial septal brain regions at the source of cholinergic projections to cortex and hippocampus. The representative cholinergic nicotinic and muscarinic receptor agonists nicotine (0.1 mg/kg) and arecoline (1.0 mg/kg) were also tested for comparison. Both arecoline and nicotine improved initial acquisition in rats before lesioning, in terms of latency to find a hidden platform and accuracy of search strategy. WAY100289 did not affect the performance of normal rats significantly, apart from some non-significant trends towards improvement with the highest dose. However, in animals showing transient navigational deficits in retention and relearning after lesioning, WAY100289 improved performance at all three doses, though ameliorative effects of nicotine and arecoline were more marked also in lesioned rats. These results show that WAY100289 improved spatial learning in animals impaired after lesions to cholinergic projection nuclei, which may reflect an interaction with cholinergic transmission to enhance cognitive function. However, in the present study, WAY100289 appeared to be less effective than direct cholinergic agonists.

Potentiation by viral respiratory infection of ovalbumin‐induced guinea‐pig tracheal hyperresponsiveness: role for tachykinins

Abstract: 1 We investigated whether virus-induced airway hyperresponsiveness in guinea-pigs could be modulated by pretreatment with capsaicin and whether viral respiratory infections could potentiate ovalbumin-aerosol-induced tracheal hyperresponsiveness. 2 Animals were inoculated intratracheally with bovine parainfluenza-3 virus or control medium 7 days after treatment with capsaicin (50 mg kg−1, s.c). Four days after inoculation, tracheal contractions were measured to increasing concentrations of substance P, histamine and the cholinoceptor agonist, arecoline. 3 In tracheae from virus-infected guinea-pigs, contractions in response to substance P, histamine and arecoline were significantly enhanced (P<0.01) by 144%, 46% and 77%, respectively. Capsaicin pretreatment inhibited the hyperresponsiveness to substance P partly (62%) and to histamine and arecoline completely. 4 In another series of experiments animals were first sensitized with ovalbumin (20 mg kg−1, i.p.). After 14 days animals were exposed to either saline or ovalbumin aerosols for 8 days. After 4 aerosol exposures (4 days) animals were inoculated with either parainfluenza-3 virus or control medium. One day after the last ovalbumin aerosol, tracheal contraction in response to increasing concentrations of substance P, histamine and arecoline was measured. 5 Tracheae from ovalbumin-aerosol-exposed control inoculated animals showed a similar degree of airway hyperresponsiveness to saline-aerosol-exposed virus-treated guinea-pigs. Virus inoculation of ovalbumin-treated animals significantly potentiated the tracheal contractions to substance P compared to either of the treatments alone. The contractions in response to histamine and arecoline were only slightly enhanced. 6 In conclusion, sensory nerves and/or tachykinins are involved in virus-induced airway hyperresponsiveness in guinea-pigs and viral respiratory infections can potentiate the increase in tracheal responsiveness to bronchoconstrictor agonists after ovalbumin exposure.

Lead-induced changes in muscarinic cholinergic sensitivity.

Abstract: This study was undertaken to determine whether the biochemical changes in cholinergic systems produced by lead exposure result in corresponding changes in cholinergic sensitivity in vivo. Rats chronically exposed from weaning to 0, 50 or 150 ppm lead (Pb) acetate in drinking water were trained to discriminate the stimulus properties of a dose of 1.75 mg/kg of the muscarinic cholinergic agonist, arecoline, from saline, using standard operant food reinforced drug discrimination procedures. Following acquisition of the discrimination, various doses of arecoline, another muscarinic agonist, oxotremorine, a nicotinic agonist, nicotine, and the GABAA modulator, pentobarbital, were substituted for the arecoline training dose, and the ability of various doses of the muscarinic antagonist, atropine, to antagonize the discriminative stimulus properties of the 1.75 mg/kg dose of arecoline were examined. Arecoline and oxotremorine produced dose-related increases in drug lever responding, while pentobarbital produced a partial generalization that was not dose-related. Arecoline's stimulus properties were substantially antagonized by atropine. Pb exposure significantly increased sensitivity to oxotremorine but not to arecoline, and attenuated the ability of some doses of atropine to antagonize the stimulus properties of arecoline. These findings demonstrate altered cholinergic sensitivity in response to environmentally relevant levels of lead in blood, and raise the possibility of cholinergic system disturbances in the behavioral manifestations produced by lead exposure.

Growth of oral and skin fibroblasts from patients with oral submucous fibrosis

Abstract: The purpose of the investigation was to evaluate and compare the proliferation (growth) of mouth fibroblasts and skin fibroblasts from patients with oral submucous fibrosis (OSF). Material comprised fibroblasts from fibrous bands situated in the buccal mucosa and from the inner aspect of the forearm of 8 patients with classic features of OSF as well as fibroblasts from 6 buccal mucosa and 8 skin biopsy specimens from healthy non-areca nut chewing individuals. Cells were cultured for 8 days according to standard techniques. Their growth was monitored daily, under optimal conditions as well as exposure to concentrations of arecoline. The data were analyzed using regression analysis, analysis of variance and the Kruskal-Wallis test. We found no statistically significant differences between the proliferation patterns of oral and skin fibroblasts from patients or between those from patients and controls. The reaction of the cells exposed to concentrations of arecoline was similar; at low concentrations (0.1-10 micrograms/ml) normal growth was maintained, while 100 micrograms/ml inhibited growth. It is concluded that fibroblasts from mouths affected by OSF have proliferation patterns which fall within normal parameters, that the excessive collagen formation in established OSF is not due to increased fibroblast proliferation and that arecoline does not stimulate fibroblast proliferation.

In vitro production of interleukin-6 by human gingival, normal buccal mucosa, and oral submucous fibrosis fibroblasts treated with betel-nut alkaloids.

Abstract: This study aimed to assess the possibility of a direct effect of betel-nut alkaloids arecoline and arecaidine on cell proliferation and interleukin-6 (IL-6) production by cultured fibroblasts from human normal gingiva, buccal mucosa and oral submucous fibrosis (OSF) buccal mucosa in vitro. Confluent monolayers of fibroblasts were incubated with or without alkaloids in the presence of 10% fetal calf serum for 48 h at 37 degree C in 5% CO2 and air. At the end of the culture period, supernatants were collected and assayed for IL-6 level. The cell proliferation was monitored by determining 5-bromo-2'-deoxy-uridine (BrdU) incorporated into cellular DNA. Except for the fact that arecoline inhibited cell growth at 100 micrograms/ml, arecoline and arecaidine had similar dose-dependent stimulant effects on the proliferation of these three groups fibroblasts. Concentrations of IL-6 in the control culture supernatants were greatest in healthy gingival fibroblasts, followed by normal buccal mucosa and OSF. Also, the presence of fetal calf serum could stimulate IL-6 release. Except for arecoline at the 100 microgram/mg, there were no significant differences in IL-6 levels between treated and control cultures of the same group when the data were expressed with mean +/- S.D.. However, two of six individuals' normal buccal mucosa fibroblasts significantly released less IL-6, and some cases of OSF and healthy gingiva exhibited slightly higher levels of IL-6 when cells were exposed to arecoline or arecaidine in cultures. Such findings suggests that arecoline and arecaidine can enhance cell proliferation and affect fibroblasts to synthesize IL-6. Furthermore, IL-6 may be a contributing molecular factor in the pathological features noted in OSF.