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Effect of pertussis toxin on the heart muscarinic-cholinergic receptors and their function
Authors:J L Boyer  M Martínez-Cárcamo  A Monroy-Sánchez  J Juárez-Ayala  G Pastelín  C Posadas  J A García-Sáinz
Affiliation:1. Departamento de Bioenergética, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. Apartado Postal 70-600; 04510 México D.F., USA;2. Departamento de Endocrinología, USA;3. Departamento de Farmacología, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano #1, 14080 México D.F., USA;1. Eye Unit, University Hospital Maggiore della Carità, Novara, Italy;2. Department of Ophthalmology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK;3. Beetham Eye Institute, Joslin Diabetes Centre, Harvard Medical School, Boston, MA, USA;4. Philippine Eye Research Institute, University of the Philippines, Manila, Philippines;5. Diabetes and Metabolism Research Unit, Vall d''Hebron Research Institute, Barcelona, Spain;6. Department of Medicine and Endocrinology, Autonomous University of Barcelona, Barcelona, Spain;7. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain;8. Centre for Public Health, Queen''s University Belfast, Belfast, UK;1. Department of Ophthalmology and Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA;2. Department of Ophthalmology and Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA;3. Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA;4. Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA;5. Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA
Abstract:Administration of pertussis toxin to rats induced a significant increase in heart rate that was evident as soon as 24 hours after the administration of the toxin and that persisted for at least 15 days. Electrical stimulation of the vagus decreased dramatically the heart rate of control animals but was unable to do it so in rats treated with pertussis toxin. In cardiac membranes muscarinic agonists decreased adenylate cyclase activity (approximately equal to 20-25%); no effect was observed in membranes obtained from toxin-treated animals. Agonist displacement of antagonist binding [( 3H] Quinuclidinyl benzilate) indicated that treatment with pertussis toxin decreased the proportion of receptors in the high affinity state for agonists. All these data suggest that blockade of the parasympathetic tone plays a key role in the induction of tachycardia by pertussis toxin.
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