Endothelial serotonin uptake and mediation of prostanoid secretion and stress fiber formation.
The kinetics of serotonin (5-hydroxytryptamine [5-HT] ) uptake by intimal and microvessel endothelial cells (ECs), in culture and in suspension, were investigated. The data suggest that although the amine is cleared rapidly by all types of ECs, the mode of uptake varies according to endothelial source. Confluent cultured aortic ECs clear exogenous 5-HT by a nonsaturable mechanism. Cardiac microvessel ECs also clear 5-HT by nonmediated diffusion, unlike pulmonary and adipose microvascular ECs, where a carrier-mediated mechanism exists. The action of 5-HT on prostanoid secretion and prostacyclin (prostaglandin I2 [PGI2] ) on 5-HT uptake by primary cultures of confluent aortic ECs was assayed. In vitro 5-HT concentrations from 10(-3) to 10(-12) M have no effect on PGI2 and thromboxane (TxA2) synthesis by cultured primary aortic ECs. Exogenous PGI2, however, inhibits 5-HT uptake by cultured primary aortic ECs. Last, 5-HT stimulates stress fibers as much as 80%, and increases surface area by 40% in cultured ECs. The agonistic action of 5-HT appears to be receptor mediated in that it can be blocked by pretreating the ECs with ketanserin, a 5-HT2 receptor blocker. Prostanoids also mediate stress fiber numbers, and substances known to increase permeability such as TxA2 also cause a disassembly of stress fibers. We hypothesize that 5-HT and PGI2, by some mechanism yet to be explained, directly and/or indirectly help to maintain endothelial structural integrity by promoting stress fiber formation.
D000818:Animals; D001692:Biological Transport; D002196:Capillaries / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*
D013931:Thromboxanes; D012701:Serotonin; D013928:Thromboxane A2; D011464:Epoprostenol