icatibant and phorbolol-myristate-acetate

Through inhibitory and excitatory effects on sympathetic neurons, B(2) bradykinin receptors contribute to protective and noxious cardiovascular mechanisms. Presynaptic inhibition of sympathetic transmitter release involves an inhibition of Ca(V)2 channels, neuronal excitation an inhibition of K(V)7 channels. To investigate which of these mechanisms prevail over time, the respective currents were determined. The inhibition of Ca(2+) currents by bradykinin reached a maximum of 50%, started to fade within the first minute, and became attenuated significantly after > or = 4 min. The inhibition of K(+) currents reached a maximum of 85%, started to fade after > 3 min, and became attenuated significantly after > or = 7 min. Blocking Ca(2+)-independent protein kinase C (PKC) enhanced the inhibition of Ca(2+) currents by bradykinin and delayed its fading, left the inhibition of K(+) currents and its fading unaltered, and enhanced the reduction of noradrenaline release and slowed its fading. Conversely, direct activation of PKC abolished the inhibition of noradrenaline release and largely attenuated the inhibition of Ca(2+) currents. These results show that the inhibitory effects of bradykinin in sympathetic neurons are outweighed over time by its excitatory actions because of more rapid, PKC-dependent fading of the inhibitory response.

Topics: Adrenergic beta-Antagonists; Animals; Animals, Newborn; Bradykinin; Calcium; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Inhibitors; Indoles; Maleimides; Membrane Potentials; Neural Inhibition; Neurons; Norepinephrine; Patch-Clamp Techniques; Protein Kinase C; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Sodium Channel Blockers; Statistics, Nonparametric; Superior Cervical Ganglion; Tetradecanoylphorbol Acetate; Tetrodotoxin; Time Factors; Tritium