Article date: February 1996
By: Sadaharu Usune, Takeshi Katsuragi, Tatsuo Furukawa, in Volume 117, Issue 4, pages 698-702
The contraction and intracellular Ca2+ change evoked by diadenosine tetraphosphate (AP4A) were studied in the outer longitudinal muscle of the guinea‐pig urinary bladder and compared with those evoked by ATP and αβ‐methylene ATP (a P2‐purinoceptor agonist).
AP4A, ATP and α,β‐methylene ATP produced concentration‐dependent transient contractions. These contractions were inhibited by PPADS (pyridoralphosphate‐6‐azophenyl‐ 2′‐4′‐disulphonic acid), 0.3–30 μm, a P2X‐purinoceptor antagonist, and suramin, 1–300 μm, a P2‐purinoceptor antagonist in a concentration‐dependent manner. From Schild plot analysis, the apparent pA2 values for PPADS for contractions evoked by AP4A, ATP and α,β‐methylene ATP were 6.86, 6.56, 6.74, and those for suramin were 6.01, 4.59 and 5.12, respectively; the Schild slopes for PPADS were 1.07, 1.14 and 1.06, and, those for suramin 0.75, 1.05 and 1.16, respectively.
AP4A (10 μm) and ATP (100 μm) failed to elicit any contraction of the tissue after a desensitization produced by repeated application of α,β‐methylene ATP (1 μm).
In fluorescence experiments with fura‐2, the increases in [Ca2+]i and contraction evoked by AP4A were suppressed by suramin and nifedipine, an L‐type Ca2+ channel blocker.
These findings suggest that P2X‐purinoceptors, which are more sensitive to PPADS than suramin, exist on the outer longitudinal muscles of guinea‐pig urinary bladder, and that the AP4A‐evoked contraction results from Ca2+ influx.
The contraction and intracellular Ca2+ change evoked by diadenosine tetraphosphate (AP4A) were studied in the outer longitudinal muscle of the guinea‐pig urinary bladder and compared with those evoked by ATP and αβ‐methylene ATP (a P2‐purinoceptor agonist).
AP4A, ATP and α,β‐methylene ATP produced concentration‐dependent transient contractions. These contractions were inhibited by PPADS (pyridoralphosphate‐6‐azophenyl‐ 2′‐4′‐disulphonic acid), 0.3–30 μm, a P2X‐purinoceptor antagonist, and suramin, 1–300 μm, a P2‐purinoceptor antagonist in a concentration‐dependent manner. From Schild plot analysis, the apparent pA2 values for PPADS for contractions evoked by AP4A, ATP and α,β‐methylene ATP were 6.86, 6.56, 6.74, and those for suramin were 6.01, 4.59 and 5.12, respectively; the Schild slopes for PPADS were 1.07, 1.14 and 1.06, and, those for suramin 0.75, 1.05 and 1.16, respectively.
AP4A (10 μm) and ATP (100 μm) failed to elicit any contraction of the tissue after a desensitization produced by repeated application of α,β‐methylene ATP (1 μm).
In fluorescence experiments with fura‐2, the increases in [Ca2+]i and contraction evoked by AP4A were suppressed by suramin and nifedipine, an L‐type Ca2+ channel blocker.
These findings suggest that P2X‐purinoceptors, which are more sensitive to PPADS than suramin, exist on the outer longitudinal muscles of guinea‐pig urinary bladder, and that the AP4A‐evoked contraction results from Ca2+ influx.
DOI: 10.1111/j.1476-5381.1996.tb15246.x
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