autacoids(自泌物).pptVIP

Histamine and Histamine Antagonists GAO Fen-Fei Histamine Histamine is one of the most important autacoids(自泌物), and is formed from the amino acid histidine(组氨酸) and is stored in high concentrations in mast cells, and basophils(嗜碱细胞). Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter. It may play a role in many brain functions such as neuroendocrine control, cardiovascular regulation, thermoregulation, and arousal. A second important nonneuronal site of histamine storage and release is the enterochromaffin(肠嗜铬)-like (ECL) cell of the fundus of the stomach.——the primary acid secretagogues(促分泌的). Receptors Effects Two receptors for histamine, H1 and H2, mediate most of the well-defined actions; H1 receptor: important in smooth muscle effects, especially those caused by IgE-mediated responses. IP3 and DAG are released. Bronchoconstriction and vasodilation. Vasodilation by release of endothelium-derived relaxing factor (EDRF), are typical responses of smooth muscle. Capillary endothelium, in addition to releaseing EDRF, also contracts, opening gaps in the permeability barrier and resulting in the formation of local edema. H2 receptor: activation of adenylyl cyclase → cAMP↑ Mediates gastric acid secretion by parietal cells in the stomach. Cardiac stimulant(强心剂) effect. Reduce histamine release from mast cells——a negative feedback effect. H3 receptor: involved mainly in presynaptic modulation of histaminergic neurotransmission in the central nervous system. In the periphery, it appears to be a presynaptic heteroreceptor with modulatory effects on the release of other transmitters. Tissues and Organ System Effects of Histamine Exerts powerful effects on smooth and cardiac muscle, on certain endothelial and nerve cells, and on the secretory cells of the stomach. Sensitivity to histamine varies greatly among species. Humans, guinea pigs, dogs, and cats are quite sensitive, while mice and rats are much