Interactions between forskolin, calcium and Bay K 8644 in K+-depolarized rat uterine muscle

1. Forskolin (FORS) (0.03 to 10 microM) caused a concentration-dependent rightward shifts of the dose-response curves to CaCl2 in the isolated K+-depolarized rat uterus, with apparent, pA2 value of 8.3, but the slope was different from unity (0.55). 2. In presence of Bay K 8644 (10 and 100 nM), the pA2 values for FORS against CaCl2 contractions were reduced in a concentration-dependent manner and increased the slopes of Schild plots to values no longer different from unity. 3. In presence of low Ca2+ concentration (0.22 nM), the potency of FORS in antagonizing CaCl2 contractions was reduced in about 2-fold. 4. FORS (0.3-3 microM) caused a dose- and time-dependent relaxation of sustained contraction induced by CaCl2 (0.5 mM). 5. FORS (0.3 microM) like nifedipine (NIF, 30 pM) caused a concentration-dependent displacement to the right of the dose-response curve to Bay K 8644 (0.1-100 nM) in K+-depolarized preparations. 6. Higher concentration of both FORS (1 and 3 microM) and NIF (0.01 and 0.03 nM) also reduced the maximal response of Bay K 8644. 7. Both drugs caused a concentration-dependent relaxation of uterine muscle contracted by Bay K 8644 (100 nM) and K+ (80 nM), but neither FORS nor NIF discriminated the two types of contraction.