Serotonergic prejunctional inhibition of canine coronary adrenergic nerves.

The actions of 5-hydroxytryptamine (5-HT) on the response of isolated canine coronary arteries to adrenergic nerve stimulation and norepinephrine were studied. 5-HT inhibited the beta adrenergic relaxation of left circumflex coronary rings in response to transmural electrical stimulation. The sensitivity to exogenously added norepinephrine was unaffected, suggesting that the effect on the response to electrical stimulation is prejunctional. Inhibition of norepinephrine release by 5-HT was confirmed in strips of coronary artery preincubated in [3H]norepinephrine. Serotonergic antagonists were tested for their ability to block the prejunctional inhibition by 5-HT, as well as their effects on the response of the coronary artery to electrical stimulation and norepinephrine. The nonselective serotonergic antagonists, methiothepin and metergoline, but not the selective 5-HT2 antagonists, ketanserin and LY 53857, prevented the inhibition by 5-HT of the response to electrical stimulation and of the stimulated overflow of [3H]norepinephrine. All of the serotonergic antagonists studied had additional effects on the response of the coronary artery to electrical stimulation or to norepinephrine. However, the alpha adrenergic antagonist, phentolamine, had additional effects similar to the serotonergic antagonists, but did not antagonize prejunctional inhibition caused by 5-HT. Furthermore, methiothepin did not block prejunctional inhibition caused by acetylcholine, suggesting the specificity of the nonselective serotonergic antagonists. Because the prejunctional inhibition by 5-HT was unaffected by neuronal uptake blockade with cocaine, these results suggest specific, non-5-HT2 serotonergic receptors on coronary adrenergic nerves which, when activated, inhibit the stimulated release of norepinephrine.