[Effects of modulators of calcium metabolism on mesenteric artery contractions during activation of P2X receptors in guinea-pig].
ATP evokes changes in the vascular tone through the activation of P2X and P2Y purinoceptors. To evaluate relative contribution of Ca2+ entry through the L-type voltage-gated calcium channels and Ca2+ -induced Ca2+ -release (CICR) mechanisms in initiation of vascular smooth muscle contraction induced by P2XRs activation, we have applied P2X receptor agonist -meATP (10 microM) and measured changes in phasic isometric tension of endothelium-denuded mesenteric artery rings in the presence of antagonists IP3Rs (60 mcmol/l APB) or RyRs (100 mcmol/l tetracaine) combined with on-off modulation of the L-type calcium channels by nicardipine (5 microM). We found that activation of P2XRs results in Ca2+ release from SR through both IP3Rs and RyRs. In addition, Ca2+ entry via L-type Ca2+ channels also participates in Ca2+ release from SR presumably through CICR mechanism. However, the phasic contractions in the presence of nicardipine were found to be less sensitive to inhibition of IP3Rs than RyRs (47.1 +/- 9.5% and 22.9 +/- 1.4% comparing to 38.3 +/- 9.6% and 518 +/- 7.8% in control solution for IP3R and RyR inhibition, respectively). This finding suggests that Ca2+ entered the cell through L-type Ca2+ channels, has easier access to IP3Rs than to RyRs. This suggestion is further supported by immunostaining IP3Rs and RyRs. Confocal imaging revealed that sub-PM SR elements are enriched with IP3Rs, while RyRs are predominantly located in the central/perinuclear SR elements.
Sukhanova
Kh Iu
KhIu
Buryĭ
V A
VA
Sahach
V F
VF
Bolton
T B
TB
Hordiienko
D V
DV
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D053496:Inositol 1,4,5-Trisphosphate Receptors; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D019837:Ryanodine Receptor Calcium Release Channel; D000255:Adenosine Triphosphate; D009529:Nicardipine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium