P2-purinergic receptor antagonists reduce the minimum alveolar concentration of inhaled volatile anesthetics.
In the central nervous system (CNS), adenosine triphosphate (ATP) is reported to serve as a fast excitatory neurotransmitter via P2X receptor. To examine possible involvement of inhibition of ATP signal-transmission in anesthetic mechanism, the effect of intracerebroventricular (ICV) administration of P2 receptor antagonists on the minimum alveolar concentration (MAC) of sevoflurane and isoflurane was studied in rat. ICV administration of P2 receptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), significantly reduced MAC of both anesthetics. The reduction of the MAC by both suramin and PPADS was dose-dependent and reached plateau at 150 microgram/rat. These results suggest that the inhibition of ATP-signal transmission may be involved in analgesic or anesthetic effect in brain.
Masaki
E
E
Department of Pharmacology (I), Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, Japan. jkyakuri@sepia.ocn.ne.jp
Ebisawa
T
T
Kondo
I
I
Hayashida
K
K
Matsumoto
Y
Y
Kawamura
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems; D004347:Drug Interactions / Q000502:physiology; D005740:Gases / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D018685:Anesthetics, Inhalation; D000970:Antineoplastic Agents; D005740:Gases; D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D000077149:Sevoflurane; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D007530:Isoflurane