Priming interactions between platelet activating factor and histamine in the in vivo microcirculation.
To elucidate whether priming exists between platelet-activating factor (PAF) and histamine in the microcirculation, we measured the clearance of FITC-dextran 150 in response to the topical applications of substimulatory concentrations of PAF and histamine. Maximal priming by PAF was observed when a 5-min interval separated the applications of 10(-9) M PAF and 10(-6) M histamine. The mean (+/- SEM) clearance resulting from this sequence of agonist administration was 7529 +/- 659 nl.2 h-1.g-1, representing a 4.5-fold enhancement in FITC-dextran 150 clearance compared with that evoked by 10(-6) M histamine alone (1664 +/- 397 nl.2 h-1.g-1). Lowering the PAF priming dose to 10(-11) M, or reversing the order of agonist addition to the microcirculation, resulted in diminished but significant responses of 3545 +/- 1143 and 4467 +/- 1170 nl.2 hr-1.g-1, respectively. Coapplication of PAF and histamine or increasing the time interval between the agonists to 15 min greatly reduced the responses to 1906 +/- 678 and 2770 +/- 837, respectively. The PAF receptor antagonist WEB 2086 (2 mg/kg i.v.), the H1 blocker pyrilamine (10 mg/kg i.v.), and leukocyte depletion with cyclophosphamide (150 mg/kg i.p.) completely abolished the PAF priming effect. In addition, the 5-lipoxygenase inhibitor RG 5901 (1 or 10 mg/kg i.v.) produced a two-thirds attenuation in PAF priming. We conclude that 1) PAF has the ability to prime the in vivo microvascular actions of histamine in both a concentration and time-dependent fashion; 2) this primed response is receptor mediated; and 3) histamine can prime the microcirculation for enhanced responses to PAF. Our data also demonstrate that leukocytes and the release of leukotrienes participate in PAF priming.
Tomeo
A C
AC
Department of Physiology, UMDNJ-New Jersey Medical School, Newark 07103-2714.
Egan
R W
RW
Durán
W N
WN
D000818:Animals; D006224:Cricetinae; D006632:Histamine / Q000097:blood* / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007970:Leukopenia / Q000097:blood; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000737:chemistry; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled
D006633:Histamine Antagonists; D015289:Leukotrienes; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D006632:Histamine