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Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 296:H1141-H1149
- Publication Year :
- 2009
- Publisher :
- American Physiological Society, 2009.
-
Abstract
- Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O2C) were studied in awake mice lacking one or both of the adenosine A1 or A2A receptors (A1R or A2AR, respectively) using telemetry and respirometry, before and after caffeine administration. All parameters were lower during day than night and higher in females than males. When compared with wild-type (WT) littermates, HR was higher in male A1R knockout (A1RKO) mice but lower in A2ARKO mice and intermediate in A1-A2AR double KO mice. A single dose of an unselective β-blocker (timolol; 1 mg/kg) abolished the HR differences between these genotypes. Deletion of A1Rs had little effect on Temp, whereas deletion of A2ARs increased it in females and decreased it in males. A1-A2ARKO mice had lower Temp than WT mice. LA was unaltered in A1RKO mice and lower in A2ARKO and A1-A2ARKO mice than in WT mice. Caffeine injection increased LA but only in mice expressing A2AR. Caffeine ingestion also increased LA in an A2AR-dependent manner in male mice. Caffeine ingestion significantly increased O2C in WT mice, but less in the different KO mice. Injection of 30 mg/kg caffeine decreased Temp, especially in KO mice, and hence in a manner unrelated to A1R or A2AR blockade. Selective A2B antagonism had little or no effect. Thus A1R and A2AR influence HR, Temp, LA, and O2C in mice in a sex-dependent manner, indicating effects of endogenous adenosine. The A2AR plays an important role in the modulation of O2C and LA by acute and chronic caffeine administration. There is also evidence for effects of higher doses of caffeine being independent of both A1R and A2AR.
- Subjects :
- Male
medicine.medical_specialty
Receptor, Adenosine A2A
Physiology
Ratón
Adrenergic beta-Antagonists
Biology
Body Temperature
Mice
chemistry.chemical_compound
Oxygen Consumption
Heart Rate
Caffeine
Physiology (medical)
Internal medicine
Heart rate
medicine
Animals
Receptor
Mice, Knockout
Sex Characteristics
Dose-Response Relationship, Drug
Receptor, Adenosine A1
Articles
Adenosine
Adenosine receptor
Mice, Inbred C57BL
Dose–response relationship
Endocrinology
chemistry
Models, Animal
Knockout mouse
Timolol
Central Nervous System Stimulants
Female
Cardiology and Cardiovascular Medicine
Locomotion
medicine.drug
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....ba4e8d43408db10930eb23d465f796ce