Effects of tryptamine mediated through 2 states of the 5-HT2 receptor in calf coronary artery.

The mode of action of tryptamine was investigated on strips of left circumflex coronary artery of calf. 1) Exposure to (-)-deprenyl, an irreversible inhibitor of monoamine oxidase B, markedly potentiated the contractions caused by tryptamine but not those by 5-hydroxy-tryptamine (5-HT). Experiments were therefore carried out on arteries treated with (-)-deprenyl. 2) Tryptamine, administered non-cumulatively, elicited fast developing contractions, which partially faded. The intrinsic activity for the peak response to tryptamine was 0.8 compared to 5-HT. Ketanserin competitively antagonized the tryptamine-induced contractions with a KB of (-log mol/l) 9.9. Methysergide antagonized the effects of tryptamine in a noncompetitive manner by depressing the maximum response with an IC50 (-log mol/l) greater than 9.0. 3) Tryptamine caused unsurmountable depression of 5-HT-induced contractions with an IC50 (-log mol/l) of 6.4. Ketanserin also competitively antagonized the depressant effects of tryptamine on 5-HT-induced contractions with a KB of (-log mol/l) 9.9. 4) At high concentrations of tryptamine (0.2-1 mmol/l), the fast developing contractions were followed by slowly developing contractions. Methysergide 1 nmol/l enhanced maximally the slow developing contractions. 5) These findings are consistent with an interaction of tryptamine at different sites of the allosteric 5-HT2-receptor system: (I) Tryptamine competes with ketanserin for the 5-HT2-receptor in the highly active R state. Binding of tryptamine to the R state would cause the fast contraction. (II) Tryptamine competes with ketanserin for the allosteric sites.(ABSTRACT TRUNCATED AT 250 WORDS)