Platelet-mediated vascular permeability in the rat: a predominant role for 5-hydroxytryptamine.
The intradermal injection in rat skin of washed, thrombin-activated platelets produces an increase in vascular permeability, the intensity of which increments with the platelet concentration. Pretreatment of the recipient animals with serotonergic antagonists, including the specific 5-HT2 receptor blocker ketanserin, potently inhibits the platelet-mediated and the 5-HT-induced vascular defect. Amine depletion of platelets or skin tissues with reserpine reduces the response to platelets. Platelet prostanoid and lipoxygenase derivatives play no major role in the vascular response to platelet. The permeability increase induced by exogenous 5-HT and by activated platelets is reduced by alpha 1-adrenergic stimulation with noradrenaline or phenylephrine and by beta 2-stimulation with terbutaline or isoprenaline, and is potentiated by adenosine; this points to a modulation of permeability by blood flow changes and to a direct beta-adrenergic effect at the endothelial cell membrane. This study demonstrates a predominant role for 5-HT in the platelet-mediated vascular permeability increase in a sensitive species like the rat.
De Clerck
F
F
Van Gorp
L
L
Beetens
J
J
Reneman
R S
RS
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013496:Suprofen / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D010880:Piperidines; D016718:Arachidonic Acid; D012701:Serotonin; D006632:Histamine; D007650:Ketanserin; D013496:Suprofen; D013917:Thrombin