High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.
The salivary glands of Rhodnius prolixus contain a nitrosyl-heme protein, named nitrophorin, that releases the vasodilatory and antiplatelet compound nitric oxide (NO). Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins. Both imidazole and histamine, but not histidine can produce full of the difference spectra of the Soret band in the 1-3 microM concentration range (at a heme protein concentration of 0.4 microM). The apparent K0.5 for the binding of histamine with the heme protein is below 1 microM. Furthermore, the complex histamine-heme protein does not dissociate after molecular sieving chromatography. To investigate whether histamine could displace NO from the native nitrosyl nitrophorins, histamine was added to the native heme proteins, leading to displacement of the bound NO as observed by changes in the absorption spectra as well as by the production of nitrite. Finally, the antihistamine effect of the heme protein was demonstrated by its inhibition of the histamine-provoked contractures of the guinea pig ileum. It is concluded that histamine, a common autacoid found at the site of injury and exposure to antigenic substances such as the site of feeding by hematophagous arthropods, can be scavenged by the nitrosyl nitrophorin of R. prolixus, which, in return, will release the vasodilatory and platelet inhibiting NO to counteract the host hemostatic response.
Ribeiro
J M
JM
Department of Entomology, University of Arizona, Tucson 85721.
Walker
F A
FA
D000818:Animals; D002850:Chromatography, Gel; D004578:Electron Spin Resonance Spectroscopy; D006168:Guinea Pigs; D006420:Hemeproteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding; D012239:Rhodnius / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
D006420:Hemeproteins; D006633:Histamine Antagonists; D007093:Imidazoles; D012471:Salivary Proteins and Peptides; C090560:nitrophorin; D009569:Nitric Oxide; C029899:imidazole; D006632:Histamine