Inhibition of adrenergic neurotransmission in canine tibial artery after exposure to 5-hydroxytryptamine in vitro.
Blood vessels may be exposed to 5-hydroxytryptamine when platelets aggregate and release vasoactive substances at sites of damage or disease. The functional consequences were studied of exposing the dog tibial artery for 2 hr to 5-hydroxytryptamine (10(-6) M) in vitro. During the exposure, unmetabolized 5-hydroxytryptamine was accumulated by the cocaine-sensitive amine uptake mechanism of tibial artery adrenergic nerves. After exposure to [3H]-5-hydroxytryptamine, transmural electrical stimulation caused the release of the tritiated indoleamine which was blocked by tetrodotoxin. After a 1-hr washout of rings of tibial artery exposed previously to 5-hydroxytryptamine, contractions in response to transmural electrical stimulation were depressed, whereas the response to exogenously added norepinephrine was unaffected. That the decreased response to electrical stimulation after exposure to 5-hydroxytryptamine was due to decreased release of norepinephrine from adrenergic nerves was demonstrated in strips of the artery preincubated in [3H]norepinephrine. The inhibition of [3H]norepinephrine release after exposure to 5-hydroxytryptamine, was blocked by the serotonergic antagonist, methiothepin, but not by the alpha adrenergic antagonist, phentolamine, suggesting that serotonergic receptors mediate the inhibition. The inhibition of [3H]norepinephrine release also was prevented by blocking adrenergic neuronal uptake with cocaine before exposure to 5-hydroxytryptamine. These results suggest that 5-hydroxytryptamine is accumulated and released by tibial artery adrenergic nerves as a cotransmitter. In so doing, the indoleamine inhibits adrenergic neurotransmission in the tibial artery by its action at prejunctional serotonergic receptors.
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000294:innervation / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013977:Tibia / Q000098:blood supply*
D000588:Amines; D007211:Indoles; C026785:5-hydroxyindole; D012701:Serotonin; D008719:Methiothepin; D003042:Cocaine; D009638:Norepinephrine; D010646:Phentolamine