Opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression does not involve a pertussis toxin-sensitive G protein.
Whether the opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression involves a pertussis toxin (PTX)-sensitive G protein was investigated in pithed rats. Adenosine and levcromakalim were used as reference substances. The blood pressure of pithed rats was kept elevated with an i.v. infusion of methoxamine. 2-(1-Octynyl)-adenosine (YT-146; 0.1-10 micrograms/kg i.v.), a selective adenosine A2 receptor agonist, produced a dose-dependent and long-lasting decrease in mean blood pressure (MBP) scarcely affecting heart rate (HR). Levcromakalim (0.3-10 micrograms/kg per min i.v. for 20 min) produced a dose-dependent and slowly developing decrease in MBP. The vasodepressor effects of YT-146 and levcromakalim were antagonized by glibenclamide (20 mg/kg i.v.), a blocker of ATP-sensitive K+ channels; the ED50 values for YT-146 and levcromakalim both increased about 2.5-fold. In rats pretreated with PTX (10 micrograms/kg i.v.), in which vagally induced bradycardia was nearly abolished, the vasodepressor effects of YT-146 and levcromakalim were slightly enhanced. Adenosine (0.3-10 mg/kg per min i.v. for 1 min) produced a dose-dependent and long-lasting decrease in MBP accompanied by a transient decrease in HR. The vasodepressor effect of adenosine was antagonized by glibenclamide; the ED50 value for adenosine increased about 3.2-fold, but not after PTX pretreatment. In contrast, the transient bradycardia was antagonized by PTX pretreatment but not by glibenclamide. These results suggest that the opening of ATP-sensitive K+ channels in vascular smooth muscle following stimulation of adenosine A2 receptors by YT-146 and adenosine does not involve a PTX-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Furukawa
S
S
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Satoh
K
K
Taira
N
N
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*; D014630:Vagus Nerve; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000480:Alkynes; D000959:Antihypertensive Agents; D015221:Potassium Channels; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; C070494:YT 146; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D005905:Glyburide