P2 receptor-mediated afferent arteriolar vasoconstriction during calcium blockade.
Experiments were performed to determine the role of L-type calcium channels on the afferent arteriolar vasoconstrictor response to ATP and UTP. With the use of the blood-perfused juxtamedullary nephron technique, kidneys were perfused at 110 mmHg and the responses of arterioles to alpha,beta-methylene ATP, ATP, and UTP were determined before and during calcium channel blockade with diltiazem. alpha,beta-Methylene ATP (1.0 microM) decreased arteriolar diameter by 8 +/- 1% under control conditions. This response was abolished during calcium channel blockade. In contrast, 10 microM UTP reduced afferent arteriolar diameter to a similar degree before (20 +/- 4%) and during (14 +/- 4%) diltiazem treatment. Additionally, diltiazem completely prevented the vasoconstriction normally observed with ATP concentrations below 10 microM and attenuated the response obtained with 10 microM ATP. These data demonstrate that L-type calcium channels play a significant role in the vasoconstrictor influences of alpha,beta-methylene ATP and ATP but not UTP. The data also suggest that other calcium influx pathways may participate in the vasoconstrictor response evoked by P2 receptor activation. These observations support previous findings that UTP-mediated elevation of intracellular calcium concentration in preglomerular vascular smooth muscle cells relies primarily on calcium release from intracellular pools, whereas ATP-mediated responses involve both voltage-dependent calcium influx, through L-type calcium channels, and the release of calcium from intracellular stores. These results support the argument that P2X and P2Y receptors influence the diameter of afferent arterioles through activation of disparate signal transduction mechanisms.
Inscho
Edward W
EW
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. einscho@mail.mcg.edu
Cook
Anthony K
AK
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; C099845:purinoceptor P2Y6; D002104:Cadmium; D000255:Adenosine Triphosphate; D004110:Diltiazem; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D014544:Uridine Triphosphate