1 A water-soluble splenic factor, which produces a contractile response of the guinea-pig ileum, that is resistant to cholinoceptor and adrenoceptor antagonists is described. 2 The ileal contractions elicited by the splenic extract showed some significant differences from those elicited by 5-hydroxytryptamine. The responses to splenic extract were not affected by the D-tryptamine-receptor antagonist, methysergide. 3 The effect of the splenic extract on the guinea-pig ileum was similar to that of histamine. The H1-histamine antagonists, (+)-chloropheniramine and diphenhydramine, caused a parallel shift to the right of the splenic extract dose-response curve without suppression of the maximum response. A pA2 value of 8.97 ± 0.03 for (+)-chloropheniramine and 7.55 ± 0.1 for diphenhydramine was calculated. 4 Significant histamine levels, as determined by fluorometric methods, could not be detected in the splenic extract. Likewise, the splenic factor did not release histamine from the intestinal preparation. 5 These results support the view that: (i) the splenic factor acts through H1-histamine receptors;(ii) it is not histamine; (iii) it does not have any histamine releasing effect on the ileal smooth muscle.
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