Effects of a 5-HT3 antagonist on peripheral 5-hydroxytryptamine-induced anorexia
Tóm tắt
Since antagonizing peripheral 5-HT2receptors incompletely blocks the anorexia induced by systemically administered 5-HT, another 5-HT receptor subtype is implicated in this effect. To determine whether the 5-HT3 receptor is the additional type involved, the specific, peripheral 5-HT3 antagonist [[3-(1-Methyl-1H-mdol-3-yl)-1,2,4-oxadiazol-5-yl]methyl]trimethyl-ammonium iodide (MIO) was used. After an overnight fast, rats were injected with MIO followed 1 h later by 5 mg/kg of 5-HT. There was a dose-dependent potentiation by MIO of the 5-HT-induced anorexia that peaked at a dose of 2.5 mg/kg of MIO. However, MIO by itself failed to induce an anorexia Although the 5-HT3 receptor is implicated in 5-HT-induced anorexia, it is suggested that its activation counters the effects of 5-HT in the mediation of the anorexia.
Tài liệu tham khảo
Bray, G. A., & York, D. A. (1972). Studies on food intake of genetically obese rats. American Journal of Physiology, 223, 176–179.
Carruba, M. O., Mantegazza, P., Memo, M., Missale, C., Pizzi, M., & Spano, P. F. (1986). Peripheral and central mechanisms of action of serotoninergic anorectic drugs. Appetite, 7(Suppl.), 105–113.
Clineschmidt, B. V., Mcguffin, J. C., Pfluger, A. B., & Totaro, J. A. (1978). A 5-hydroxytryptamine-like mode of anorectic action for 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212). British Journal of Pharmacology, 62, 579–589.
Edwards, S. (1990). The behavioural pharmacology of peripheral 5-hydroxytryptamine-induced anorexia. Unpublished doctoral dissertation, University of Nottingham.
Edwards, S., & Stevens, R. (1989). Effects of xylamidine on peripheral 5-hydroxytryptamine-induced anorexia. Pharmacology, Biochemistry & Behavior, 34, 711–720.
Edwards, S., & Stevens, R. (1991a). Effects of the peripheral 5-HT2 antagonist xylamadine on consummatory behaviors. Psychobiology, 19, 243–246.
Edwards, S., & Stevens, R. (1991b). Peripherally administered 5-hydroxytryptamine elicits the full behavioral sequence of satiety. Pharmacology, Biochemistry & Behavior, 50, 1075–1077.
Engel, G., Buchheit, K. H., & Richardson, B. P. (1989). 5-HT3 receptors in the gastrointestinal tract. In E. J. Mylenecharane, J. A. Angus, I. S. de la Lande, & P. P. A. Humphrey (Eds.), Serotonin: Actions, receptors, pathophysiology (pp. 241–248). London: Macmillan.
Fletcher, P. J., & Burton, M. J. (1984). Effects of manipulations of peripheral serotonin on feeding and drinking in the rat. Pharmacology, Biochemistry & Behavior, 20, 835–840.
Fletcher, P. J., & Burton, M. J. (1986). Dissociation of the anorectic effect of 5-HTP and fenfluramine. Psychopharmacology, 89, 216–220.
Lawton, C. L., & Blundell, J. E. (1993). 5-HT and carbohydrate suppression: Effects of 5-HT antagonists on the action of d-fenfluramine and DOI. Pharmacology, Biochemistry & Behavior, 46, 349–360.
Montgomery, A. M. H., Fletcher, P. J., & Burton, M. J. (1986). Behavioral and pharmacological investigations of 5-HT hypophagia and hypodipsia. Pharmacology, Biochemistry & Behavior, 25, 23–28.
Neill, J. C., & Cooper, S. J. (1989). Effects of 5-hydroxytryptamine and d-fenfluramine on sham feeding and sham drinking in the gastricfistulated rat. Physiology & Behavior, 46, 949–953.
Nomura, K., Maeda, N., Yoshino, T., & Yamaguchi, I. (1994). A mechanism of 5-HT3 receptor mediation is involved etiologically in the psychological stress lesion in the stomach of the mouse. Journal of Pharmacology & Experimental Therapeutics, 271, 100–106.
Oldendorf, W. H. (1971). Brain uptake of radiolabelled amino acids, amines, and hexoses after arterial injection. American Journal of Physiology, 221, 1629–1639.
Pollock, J. D., & Rowland, N. (1981). Peripherally administered serotonin decreases food intake in rats. Pharmacology, Biochemistry & Behavior, 15, 179–183.
Pratt, G. D., & Bowery, N. G. (1989). The 5-HT3 receptor ligand [3H]BRL 43694 binds to presynaptic sites in the nucleus solitarius of the rat. Neuropharmacology, 28, 1367–1376.
Pratt, G. D., Bowery, N. G., Kilpatrick, G. J., Leslie, R. A., Barnes, N. M., Naylor, R. J., Jones, B. J., Nelson, D. R., Palacios, J. M., Slater, P., & Reynolds, D. J. M. (1990). Consensus meeting agrees the distribution of 5-HT3 receptors in mammalian hindbrain. Trends in Pharmacological Sciences, 11, 135–137.
Saxena, P. R. (1989). Cardiac action of 5-hydroxytryptamine. In E. J. Mylenecharane, J. A. Angus, I. S. de la Lande, & P. P. A. Humphrey (Eds.), Serotonin: Actions, receptors, pathophysiology (pp. 115–122). London: Macmillan.
Simansky, K. J., Jakubow, J., Sisk, F. C., Vaidya, A. H., & Eberle-Wang, K. (1992). Peripheral serotonin is an incomplete signal for satiety in sham feeding rats. Pharmacology, Biochemistry & Behavior, 43, 847–854.
Swain, C. J., Baker, R., Kneen, C., Moseley, J., Saunders, J., Seeward, E. M., Stevenson, G., Beer, M., Stanton, J., & Watling, K. (1991). Novel 5-HT3 antagonists: Indole oxadiazoles. Journal of Medicinal Chemistry, 34, 140–151.
Tyers, M. B., Costall, B., & Naylor, R. J. (1989). 5-HT3 receptors in the central nervous system. In E. J. Mylenecharane, J. A. Angus, I. S. de laLande, & P. P. A. Humphrey (Eds.), Serotonin: Actions, receptors, pathophysiology (pp. 95–100). London: Macmillan.