Neuropeptide regulation of the expression of immediate hypersensitivity

Peptide mediators of sensory nerves that are released in tissues by noxious chemical and physical insults and by diverse biologic challenges rapidly elicit local and systemic responses similar to those of immediate hypersensitivity. The sensory neuropeptides have direct effects on the functions of smooth muscles, blood vessels, leukocytes, and epithelial glands and indirect effects through the actions of mediators released from mast cells stimulated by the peptides. Sensory neuropeptides exhibit cellular specificity, as exemplified by the greater potency of substance P in activating mucosal mast cells than connective tissue mast cells. The capacity of somatostatin to inhibit release of mediators from basophils challenged by IgE-dependent mechanisms, but not by basic peptides or ionophores, illustrates the biochemical specificity of the neuropeptides. The selective release of distinct sensory neuropeptides from different subsets of nerve endings, the specificity of neuropeptide recognition by mast cells, basophils, and other target cells, and the diversity of direct and indirect activities of the neuropeptides suggest that sensory nerves may initiate and modulate immediate hypersensitivity by unique mechanisms.