1 In helically-cut strips of dog coronary, superior mesenteric, right gastro-epiploic and renal arteries contracted with prostaglandin F2X (PGF21), histamine produced a dose-related relaxation, while, in contrast, the amine caused only a contraction of cerebral arterial strips. 2 The contractile response of cerebral arteries to histamine was attenuated by chlorpheniramine (10-6M) but was unaffected by cimetidine (10-5M). Relaxant responses to histamine of coronary and renal arteries were significantly attenuated by treatment with cimetidine and to a similar extent by combined treatment with cimetidine and chlorpheniramine. Chlorpheniramine alone was ineffective. 3 In mesenteric and gastro-epiploic arteries, relaxant responses to histamine were attenuated only slightly by cimetidine. Chlorpheniramine slowed the development of histamine-induced relaxations but did not alter the magnitude of the relaxations. Combined treatment with these Hl-and H2-antagonists attenuated the histamine-induced relaxations to an appreciably greater extent than treatment with cimetidine alone. 4 It may be concluded that the cerebroarterial contraction induced by histamine is mediated through HI-receptors and the relaxations of coronary and renal arteries induced by histamine are mediated through H2-receptors. It appears that Hl-and H2-receptors interact with each other to produce potentiation of histamine-induced relaxations of mesenteric and gastro-epiploic arteries.

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<p>Supplementary figure 1. Dynamic range plot of quantified Te-EV proteome. The X axis indicates abundance rank of qualified Te-EV proteome, and the Y axis indicates the relative abundance by the LC/MS analysis. Supplementary figure 2. GO analysis of up-regulated (fold change > 5, adjusted p < 0.05) and down-regulated (fold change < 0.02, adjusted p < 0.05) proteins in tumor Te-EVs. For biological process, cellular component and molecular function, data of GOTERM_BP_FAT, GOTERM_CC_FAT and GOTERM_MF_FAT were used from Gene_Ontology in Functional Annotation Tool on the website, respectively. The Y axis indicates the percentage of the annotated proteins. Supplementary figure 3. Scatter plot showing EV-CAT1 sandwich ELISA (unit) on the X axis and preoperative CEA (ng / ml) on the Y axis (left). Magnified view of the plot is also shown (right). Coefficient of correlation value was 8.5 Ã- 10-3. Supplementary figure 4. Volcano plot indicating p-value (Te-EVs vs. tissues) on the Y axis and log ratio (Te-EVs / tissue) of LC/MS intensity on the X axis. Blue dots indicate the top 100 Te-EV proteins which are significantly up-regulated than tissue proteins, and orange dots indicate the top 100 proteins which are significantly down-regulated than tissue proteins. Supplementary figure 5. The analyses of subcellular proteome localisations are shown. The subcellular locations of tissues and Te-EVs are obtained on the Uniprot website. The distribution of the two proteome is similar with each other. The numbers show percentages.</p>