Ontogeny of the smooth muscle response to histamine in rabbit and human small bowel

Histamine is known to stimulate small bowel smooth muscle contraction in adults. We studied the response to histamine of small bowel from 27 day gestation fetal (term = 31 days), 4 days-old neonatal, and weanling rabbits using an isolated muscle strip technique in vitro. Sensitivity to histamine stimulation decreased with increasing age, with a six-fold difference in mean D50 between fetal and weanling bowel. A strong contractile response was also obtained in human fetal bowel between 16 and 24 weeks gestation. The response to histamine was inhibited at all ages in both rabbit and human bowel by specific histamine H1 receptor blockade with diphenhydramine, and not by H2 or cholinergic receptor blockers. We conclude that histamine stimulates rabbit and human fetal small bowel contraction; stimulation specifically occurs via the histamine H1 receptor, and is unrelated to release of acetylcholine; sensitivity to histamine decreases significantly with maturity in the rabbit.