Control of vascular permeability and vascular smooth muscle in the respiratory tract by multiple neuropeptides.

Recent evidence suggests that a population of primary afferent neurons which terminate in the upper and lower airways contains several coexisting peptides. Thus, substance P was found to coexist with at least three structurally related tachykinins, viz. neurokinin A, neuropeptide K and an eledoisin-like peptide. Furthermore, calcitonin gene-related peptide which is structurally not related to tachykinins is also present in the same neurons which innervate a variety of peripheral tissues. Substance P, neurokinin A, eledoisin-like peptide and calcitonin gene-related peptide can simultaneously be released from central and peripheral branches of primary sensory neurons, whereas a release of neuropeptide K could not be demonstrated. Local inflammatory mediators like bradykinin or histamine also released multiple peptides in the airways and caused vascular protein leakage which is partly dependent on intact sensory nerves. In experimental animals, tachykinins as well as calcitonin gene-related peptide caused vasodilatation, whereas tachykinins but not calcitonin gene-related peptide caused an increase in vascular protein leakage. In humans, intranasally administered substance P (but not calcitonin gene-related peptide) lead to nasal obstruction as measured by rhinomanometry, and to secretion. It is suggested that activation of peripheral endings of perivascular primary sensory neurons causes vasodilatation and increase in vascular protein leakage by simultaneous action of several neuropeptides including tachykinins and calcitonin gene-related peptide.