Cyclic nucleotides augment the phasic action of tetraethylammonium on guinea-pig trachealis

It is known that after exposure to (3 mM) tetraethylammonium (TEA), guinea-pig isolated trachealis generates tonic spasm followed by phasic tension changes. We found that 8-Br-cAMP or 8-Br-cGMP (10(-6)-5 x 10(-4) M) suppressed tonic spasm secondary to TEA and induced rapid mechanical oscillations. NaN3, forskolin, aminophylline, and isoprenaline had effects similar to those of the cyclic nucleotides. Tetrodotoxin, atropine, diphenhydramine, and cimetidine were without effect on the rapid oscillations. KCl (16 mM) stimulated the oscillations in tissue treated with TEA or TEA plus 8-Br-cGMP. Diltiazem abolished all rhythmic activity in TEA plus 8-Br-cGMP-treated tissues. We conclude: (A) The rapid oscillations are a result of increased cytoplasmic calcium flux with K+ affecting the contractile arm by increasing Ca2+ entry and cyclic nucleotides affecting the relaxant arm by reducing cytosolic free Ca2+. (B) The cyclic nucleotide effect is direct. (C) Cyclic nucleotides may enhance the rate of contraction and relaxation in the presence of some forms of phasic activity.