title: Dopamine D1 receptors control exercise hyperpnoea in mice.
abstract: Previously, we undertook simultaneous recording of ventilation and pulmonary gas exchange in mice and revealed that dopamine D(2) receptors participate in exercise hyperpnoea via behavioural control of ventilation with unchanged pulmonary gas exchange. Here, we examined the hypothesis that D(1) receptors also contribute to exercise hyperpnoea using a D(1) receptor antagonist (SCH 23390; SCH) that crosses the blood-brain barrier, with the same recording technique and protocol as in the previous study. The respiratory responses of mice injected with saline or SCH (50 μg (kg body weight)(-1), i.p.) were compared during constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber equipped with a differential pressure transducer and open-circuit system with a mass spectrometer. At rest, SCH-injected mice had significantly reduced respiratory frequency, minute ventilation and pulmonary gas exchange compared with saline-injected mice. Ventilation during hyperoxic gas inhalation and hypercapnic ventilatory responses between groups were similar. Abrupt increases and sequential declines to the steady-state level were produced by treadmill exercise in both groups of mice. Treatment with SCH lowered the increased levels of respiratory frequency, tidal volume and minute ventilation during the steady state, as well as reducing the O(2) uptake, CO(2) output and body temperature throughout treadmill exercise. These data suggest that D(1) receptors contribute to a resting ventilation level and exercise hyperpnoea during the steady state in parallel with metabolic changes. Notably, the metabolic control of D(1) receptors was important for maintenance of the steady state, and D(1) receptors in hypothalamic nuclei could be involved in this modulation.
authors.affiliation: Department of Physiology, Showa University School of Medicine, Tokyo 142-8555, Japan. michiko@med.showa-u.ac.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Iwase
authors.forename: Masahiko
authors.initials: M
authors.lastname: Izumizaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Ikuo
authors.initials: I
authors.lastname: Homma
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001833:Body Temperature Regulation; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002199:Capillary Permeability; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000378:metabolism; D006935:Hypercapnia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005082:Physical Exertion; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012123:Pulmonary Ventilation / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012420:Running; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390