Doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

Abstract

To determine if doxapram stimulates the carotid body through the same mechanism as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose-dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia stimulated the carotid body. Although, doxapram had an additive effect on the carotid body chemosensory response to hypercapnia, a synergistic effect was not observed. Also, we investigated the various K(+) channel activators on the response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator; and halothane as a TASK-like background K(+) channel activator. The hypoxic response was partially reduced by halothane only, while pinacidil, levcromakalim and NS-1619 had no effect. Interestingly, the effect of doxapram was partially inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.

• Authors: Toru Takahashi, Shinobu Osanai, Hitoshi Nakano, Yoshinobu Ohsaki, Kenjiro Kikuchi
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 147 Issue 1 Pg. 1-9 (May 12 2005) ISSN: 1569-9048 [Print] Netherlands
• PMID: 15848118 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anesthetics, Inhalation
• Benzimidazoles
• Potassium Channels
• Respiratory System Agents
• Vasodilator Agents
• Cromakalim
• NS 1619
• Pinacidil
• Doxapram
• Halothane

Topics

• Anesthetics, Inhalation (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Carotid Body (drug effects)
• Carotid Sinus (drug effects, innervation)
• Cromakalim (pharmacology)
• Dose-Response Relationship, Drug
• Doxapram (pharmacology)
• Halothane (pharmacology)
• Hypoxia (physiopathology)
• Male
• Membrane Potentials (drug effects, physiology)
• Organ Culture Techniques
• Pinacidil (pharmacology)
• Potassium Channels (drug effects, physiology)
• Rabbits
• Respiratory System Agents (pharmacology)
• Vasodilator Agents (pharmacology)