Mechanism of adenosine receptor-induced renal vasoconstriction in rats.
Adenosine analogues selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), induce vasoconstriction in the isolated rat kidney perfused at constant flow. Presumably, the vasoconstriction is mediated by increased Ca2+ concentration in renal vascular smooth muscle cells, but the mechanism by which A1 adenosine receptor occupation leads to increased Ca2+ is unknown. In the present experiments, the isolated, perfused rat kidney vasoconstricted in response to CHA, to K depolarization, and to BAY K 8644 (a Ca2+ channel agonist). All of these responses were completely blocked by methoxyverapamil, which suggests that CHA, like K depolarization and BAY K 8644, induces renal vasoconstriction by increasing Ca2+ influx through potential operated Ca2+ channels. The mechanism of action of CHA was different, however, in that pertussis toxin treatment blocked the response to CHA without affecting the responses to K depolarization or to BAY K 8644. Therefore, a pertussis toxin-sensitive step must intervene between occupation of A1 adenosine receptors on renal vascular smooth muscle cells and increased Ca2+ influx through potential-operated Ca2+ channels.
Rossi
N
N
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Churchill
P
P
Ellis
V
V
Amore
B
B
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; C027513:N(6)-cyclohexyladenosine; D005711:Gallopamil; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D037342:Pertussis Toxin; D000241:Adenosine