Effects of uridine triphosphate on skinned skeletal muscle fibers of the rat.
Chemically skinned muscle fibers from rat extensor digitorum longus muscle were used to study the effects of uridine triphosphate (UTP) on Ca2+ uptake and release by the sarcoplasmic reticulum (SR) and on Ca2+-activated tensions. Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) increased submaximal Ca2+-induced tension (pCa 6.2-5.8) but diminished Po, the maximum tension elicited by pCa 4.2, by ca. 15%, (ii) markedly reduced Ca2+ uptake by the SR (evaluated by caffeine-elicited tension); and (iii) induced tension in Ca2+-loaded fibers. The UTP-induced tension averaged 55% of Po and its rates of development and decay were considerably slower than those of caffeine-evoked tension. The UTP-induced tension (i) depended on the Ca2+-loading conditions; (ii) was reversibly blocked by brief (15 s) exposures of Ca2+-loaded fibers to 5 mM EGTA or by pretreatment with caffeine; (iii) was abolished by functional disruption of the SR with the nonionic detergent Brij-58; and (iv) persisted after blockade of the SR Ca2+ release channels with ruthenium red. Exposure of Ca2+-loaded fibers to UTP depressed the tension elicited subsequently by caffeine, and enhanced the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions containing 5 mM EGTA. The UTP-induced tension is attributed to increased release of Ca2+ from the SR, via a ruthenium red insensitive pathway(s), combined with reduced Ca2+ uptake by the SR and increased Ca2+ affinity of the contractile proteins.
Suarez-Kurtz
G
G
Departamento de Bioquimica Medica, Instituto de Ciencias Biomedicas, ICB-CCS, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Rio de Janeiro, Brazil.
Catinot
M P
MP
Ponte
C G
CG
Vianna-Jorge
R
R
Mounier
Y
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004396:Coloring Agents; D004347:Drug Interactions; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D004396:Coloring Agents; D012430:Ruthenium Red; D002110:Caffeine; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate