[en] The effects of a 5-hydroxytryptamine (5-HT) challenge infusion on pulmonary function values were studied in healthy calves, pretreated with varying doses of metrenperone, a selective type 2 serotonergic (5-HT2) antagonist. In the first part of the experiment, the 5-HT challenge was performed 30 minutes after administration of metrenperone at a dose of 0.025 mg kg-1 (group 1, n = 8), 0.050 mg kg-1 (group 2, n = 8) and 0.100 mg kg-1 (group 3, n = 7). In the second part, the 5-HT challenge was performed 12 hours after administration of metrenperone at a dose of 0.050 mg kg-1 (group 4, n = 5) and 0.100 mg kg-1 (group 5, n = 5). None of the three doses of metrenperone influenced the 5-HT-induced ventilatory changes. For the challenge performed 30 minutes after blockade, all three doses inhibited the bronchoconstrictive process triggered by the 5-HT challenge. There was no dose-related inhibition. On the other hand, when the challenge was performed 12 hours after metrenperone, there was a dose-related inhibition with only the higher dose (0.100 mg kg-1) showing a significant efficacy in inhibiting 5-HT-induced bronchoconstriction. It is concluded that, if 5-HT is involved in the pathophysiological processes of respiratory diseases in cattle, a 5-HT2 blockade with metrenperone at a dose rate of 0.100 mg kg-1 and with a dosage interval of 12 hours should improve pulmonary function.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Linden, Annick ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires > Santé et pathologies de la faune sauvage
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Amory, Hélène ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Médecine interne des équidés
Rollin, Frédéric ; Université de Liège - ULiège > Département clinique des animaux de production (DCP) > Médecine interne des équidés, des ruminants et des porcs
Lekeux, Pierre ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie - Doyen de la Faculté de Médecine vétérinaire
Language :
English
Title :
Comparison of three metrenperone dosage regimens inhibiting the 5-hydroxytryptamine-induced pulmonary dysfunction in cattle
Publication date :
1993
Journal title :
Research in Veterinary Science
ISSN :
0034-5288
eISSN :
1532-2661
Publisher :
British Veterinary Association, London, United Kingdom
Aas (1983) Serotonin induced release of acetylcholine from neurons in thebronchial smooth muscle oftherat. Acta Physiologica Scandinavica 117:477-480.
Bradley, Engel, Feniuk, Fozard, Humphrey, Middelmiss, Mylecharane, Richardson, Saxena (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563-576.
Declerck, Herman (1983) 5-Hydroxytryptamine and platelet aggregation. Federation Proceedings 42:228-232.
Demling, Wong, Fox, Hechtman, Huval (1985) Relationship of increased lung serotonin levels to endotoxininduced pulmonary hypertension in sheep. American Review of Respiratory Diseases 132:1257-1261.
Dempsey, Olson, Skatrud (1986) Hormones and neurochemicals in the regulation of breathing. Handbook of Physiology , A.P. Fishman, A.B. Fisher, The respiratory system. Vol 2, Control of breathing, American Physiological Society, Bethesda, Part 1; 181-221.
Desmecht, Linden, Rollin, Amory, Lekeux (1992) Effect of intravenous and aerosol administration of 5-hydroxytryptamine on pulmonary function values in healthy calves. American Journal ofVeterinaryResearch 53:315-320.
Douglas (1985) Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. The Pharmacological Basis of Therapeutics , A.Goodman Gilman, L.S. Goodman, T.W. Rall, F. Murad, 7th edn, MacMillan, New York, Section IV, Chapter 26; 605-638.
Frazer, Maayani, Wolfe (1990) Subtypes of receptors for serotonin. Annual Review of Pharmacology and Toxicology 30:307-348.
Gilbert, Newberry (1987) A 5-HT1-like receptor mediates a sympathetic ganglionic hyperpolarisation. European Journal of Pharmacology 144:385-388.
Glennon (1987) Central serotonin receptors as targets for drug research. Journal of Medical Chemistry 30:1-12.
Hendricks (1992) Neuromuscular alterations in English bulldogs. Proceedings, 10th Comparative Respiratory Society Meeting , East Lansing; 14-17.
Huval, Lelcuk, Shepro, Hechtman (1984) Role of serotonin inpatients with acute respiratory failure. Annals of Surgery 200:166-172.
Janssen (1983) 5-HT2 receptor blockade to study serotonininduced pathology. Trends in Pharmacological Sciences 4:198-206.
Junod (1973) Uptake, metabolism, and efflux of 14C-5-hydrox-ytryptamine in isolated perfused rat lungs. Journal of Pharmacology and Experimental Therapeutics 183:341-355.
Kaumann (1983) Yohimbine and rauwolscine inhibit 5-ht-induced contraction of large coronary arteries of calf through blockade of 5-HT2 receptors. Naunyn-Schmeideberg's Archives of Pharmacology 323:149-154.
Lekeux, Hajer, Breukink (1984) Pulmonary function testing in calves: technical data. American Journal of Veterinary Research 45:342-345.
Lekeux, Hajer, Breukink (1984) Intrathoracic pressure measurement in cattle: standardization procedure. Canadian Journal of Comparative Medicine 48:420-421.
Lemoine, Kaumann (1986) Allosteric properties of 5-HT2 receptors in tracheal smooth muscle. Naunyn-Schmiedeberg's Archives of Pharmacology 333:91-97.
Leysen, De Chaffoy de Courcelles, De Clerck, Niemegeers, Van Nueten (1984) Serotonin-S2 receptor binding sites and functional correlates. Neuropharmacology 23:1493-1501.
Linden, Desmecht, Amory, Rollin, Lekeux (1993) Pulmonary response to intravenous 5-hydroxytryptamine (5HT) after 5-HT2 receptor blockade in healthy calves. Am J Vet Res, (In press); .
Macklem Procedures for standardized measurements of lung mechanics , National Heart and Lung Institute, Division of Lung Disease, Montreal, Canada; 1974, 4-5.
Monbaliu, Van Leemput, Heykants (1991) Nonclinical Pharmacokinetics Report. Report R50970/FK1252, Janssen Research Foundation. Department of Drug Metabolism and Pharmacokinetics; .
Olson (1987) Role of 5-hydroxytryptamine in endotoxin-induced respiratory failure of pigs. American Review of Respiratory Diseases 135:93-99.
Olson, Dodam (1991) Inflammatory mediators in the lung. Proceedings, 10th Comparative Respiratory Society Meeting , East Lansing; 1-21.
Paintal (1973) Vagal sensory receptors and their reflex effects. Physiological Reviews 53:159-227.
Rodarte, Rehder (1986) Dynamics of respiration. Handbook of Physiology , A.P. Fishman, A.B. Fisher, The respiratory system. Vol 3, Mechanics of breathing, American Physiological Society, Bethesda, Part 1; 131-144.
Sheller, Holtzman, Skoogh, Nadel (1982) Interaction of serotonin with vagal- and AChinduced bronchoconstriction in canine lungs. Journal of Applied Physiology: Respiration Environment Exercise Physiology 52:964-966.
Sibbald, Peters, Lindsay (1980) Serotonin and pulmonary hypertension in human septic ARDS. Critical Care Medicine 8:490-494.
Stein, Thomas (1967) Role of platelets in the acute pulmonary responses to endotoxin. Journal of Applied Physiology 23:47-52.
Thomas, Stein, Tanabe, Rege, Wessler (1964) Mechanism of bronchoconstriction produced by thromboemboli in dogs. American Journal of Physiology 206:1207-1212.
Toutain, Brandon, Alvinerie, Garcia-Villar, Ruckebusch (1982) Dexamethasone in cattle: pharamcokinetics and action on the adrenal gland. Journal of Veterinary Pharmacology and Therapy 5:33-43.
Van Nueten, Janssens, Ghoos, Schuurkes Pharmacological profile of R50970, a selective S2-serotonergic antagonist: its peripheral effects. Preclinical research report, Janssen Research Foundation, Beerse; 1987.
Van Nueten, Leysen, Vanhoutte, Janssens (1982) Serotonergicresponses in vascular and non-vascular tissues. Archives Internationales de Pharamacodynamie et de Thérapie 256:331-334.
Vincent, Degaute, Domb, Simon, Berre, Vandesteene (1984) Ketanserin, a serotonin antagonist. Administration in patients with acute respiratory failure. Chest 85:510-513.