Diminished myofibrillar sensitivity to calcium produced by simultaneous superfusion of cAMP and phosphodiesterases inhibitors in toad (Bufo arenarum Hensel) ventricle.
Experiments were performed in EGTA-skinned trabeculae from toad ventricle to explore the effects of the cAMP on calcium sensitivity of the contractile system. 10(-3) M of the cAMP derivative dibutyryl cAMP (dcAMP) failed to affect calcium sensitivity of chemically skinned ventricular trabeculae. 10(-5) M of the phosphodiesterase inhibitor isobutylmethylxantine (IBMX) produced a significant shift to the left of the tension-pCa relationship. The computed half maximally activating pCa (pCa50) were 6.32 +/- 0.03 and 6.40 +/- 0.01 in the absence and presence of IBMX respectively, (P < 0.05). Simultaneous perfusion of 10(-5) M IBMX and 10(-3) M dcAMP suppressed the leftward shift of the tension-pCa curve induced by IBMX (pCa50: 6.33 +/- 0.04 and 6.33 +/- 0.05 for control and IBMX respectively). Perfusion with the phosphodiesterase inhibitor milrinone (10(-5) M), did not produce any significant changes in the tension-pCa relationship. Simultaneous perfusion of 10(-5) M milrinone and 10(-3) M dcAMP significantly shifted to the right the tension-pCa curve. The computed pCa50 were 6.32 +/- 0.02 and 6.23 +/- 0.03 under control conditions and in the presence of dcAMP plus milrinone respectively (P < 0.05). In agreement with what has been described in mammalian heart, the results indicate that in amphibian ventricle, cAMP produced a decrease in the calcium sensitivity of the contractile proteins that is only evident in the presence of phosphodiesterase inhibitors. It is suggested that this decrease in myofilament sensitivity to calcium may be one of the mechanisms by which beta-agonists enhance myocardial relaxation in the amphibian heart.
Petroff
M V
MV
Centro de Investigationes Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Mattiazzi
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002022:Bufo arenarum; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D009210:Myofibrils / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D003994:Bucladesine; D000242:Cyclic AMP; D020105:Milrinone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine