Adenosine diphosphate potentiates the inhibition of norepinephrine-induced relaxation by 5-hydroxytryptamine in canine coronary arteries.
Vasoactive substances released from aggregating platelets inhibit beta-adrenergic neurotransmission in coronary arteries. Studies were carried out on the effects of two such vasoactive substances on canine coronary arteries, at concentrations equivalent to that released by platelets under physiological conditions. 5-Hydroxytryptamine (5 X 10(-7) M) reduced the sensitivity of coronary artery ring segments to the beta-adrenergic relaxing effects of norepinephrine. Adenosine diphosphate (3 X 10(-6) M) further reduced the sensitivity to norepinephrine caused by 5-hydroxytryptamine, while the nucleotide alone had no significant effect. 5-Hydroxytryptamine and adenosine diphosphate acted selectively on the norepinephrine-induced relaxation; whereas the relaxatory response of the vessel to nitroprusside, a direct muscle relaxant, was unaffected. 5-Hydroxytryptamine caused contraction of the tissue, but this opposing response did not account for the inhibition of the norepinephrine-induced relaxation observed in the presence of the indoleamine. The decreases in sensitivity to norepinephrine caused by 5-hydroxytryptamine and adenosine diphosphate were prevented by the serotonin receptor antagonist, methiothepin. The potentiation by adenosine diphosphate of the 5-hydroxytryptamine-induced shift in the relaxation caused by norepinephrine was blocked by the purine receptor antagonist, 8-(p-sulfophenyl)-theophylline. Neither adenosine nor alpha,beta-methylene adenosine diphosphate potentiated the action of 5-hydroxytryptamine, suggesting that phosphate hydrolysis of the nucleotide is required for the action of adenosine diphosphate. These results suggest that adenosine diphosphate potentiates the inhibitory effect of 5-hydroxytryptamine on the beta-adrenergic response of coronary arteries exposed to vasoactive substances released from platelets.
D006916:5-Hydroxytryptophan / Q000008:administration & dosage*; D000244:Adenosine Diphosphate / Q000008:administration & dosage* / Q000031:analogs & derivatives; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D066298:In Vitro Techniques; D008719:Methiothepin / Q000008:administration & dosage; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011224:Prazosin / Q000008:administration & dosage
C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D008719:Methiothepin; D000244:Adenosine Diphosphate; D006916:5-Hydroxytryptophan; D009638:Norepinephrine; D011224:Prazosin