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Anandamide modulates carotid sinus nerve afferent activity via TRPV1 receptors increasing responses to heat
- Source :
- Journal of Applied Physiology. 112:212-224
- Publication Year :
- 2012
- Publisher :
- American Physiological Society, 2012.
-
Abstract
- Abnormal respiratory chemosensitivity is implicated in recurrent apnea syndromes, with the peripheral chemoreceptors, the carotid bodies, playing a particularly important role. Previous work suggests that supraphysiological concentrations of the endocannabinoid endovanilloid and TASK channel blocker anandamide (ANA) excite carotid bodies, but the mechanism(s) and physiological significance are unknown. Given that carotid body output is temperature-sensitive, we hypothesized that ANA stimulates carotid body chemosensory afferents via temperature-sensitive vanilloid (TRPV1) receptors. To test this hypothesis, we used the dual-perfused in situ rat preparation to confirm that independent perfusion of carotid arteries with supraphysiological concentrations of ANA strongly excites carotid sinus nerve afferents and that this activity is sufficient to increase phrenic activity. Next, using ex vivo carotid body preparations, we demonstrate that these effects are mediated by TRPV1 receptors, not CB1 receptors or TASK channels: in CB1-null mouse preparations, ANA increased afferent activity across all levels of Po2, whereas in TRPV1-null mouse preparations, the stimulatory effect of ANA was absent. In rat ex vivo preparations, ANA's stimulatory effects were mimicked by olvanil, a nonpungent TRPV1 agonist, and suppressed by the TRPV1 antagonist AMG-9810. The specific CB1 agonist oleamide had no effect. Physiological levels of ANA had no effect alone but increased sensitivity to mild hyperthermia. AMG-9810 blocked ANA's effect on the temperature response. Immunolabeling and RT-PCR demonstrated that TRPV1 receptors are not expressed in carotid body glomus cells but reside in petrosal sensory afferents. Together, these results suggest that ANA plays a physiological role in augmenting afferent responses to mild hyperthermia by activating TRPV1 receptors on petrosal afferents.
- Subjects :
- Male
medicine.medical_specialty
Hot Temperature
Mice, 129 Strain
Polyunsaturated Alkamides
Physiology
medicine.medical_treatment
TRPV1
TRPV Cation Channels
Peripheral chemoreceptors
Arachidonic Acids
In Vitro Techniques
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
Physiology (medical)
Internal medicine
medicine
Animals
Neurons, Afferent
Respiratory system
Mice, Knockout
Cannabinoids
Carotid sinus
Anandamide
Endocannabinoid system
Rats
Mice, Inbred C57BL
Carotid Sinus
Endocrinology
medicine.anatomical_structure
nervous system
chemistry
lipids (amino acids, peptides, and proteins)
Carotid body
Cannabinoid
Endocannabinoids
Subjects
Details
- ISSN :
- 15221601 and 87507587
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Physiology
- Accession number :
- edsair.doi.dedup.....bb5b25332eb249b1ec43d391594c8d18