Publications

Parasympathetic nerves play an important role in modulating smooth muscle tone and mucus secretion in the airways. This modulation can occur through a variety of afferent inputs, from the central nervous system, at parasympathetic ganglia, and on post-ganglionic efferent fibres themselves. Abnormalities at any of these sites could, and in some patients probably do, contribute to the abnormalities in smooth muscle contraction and mucus secretion that characterize a number of airway diseases, including asthma. Because these pathways play little or no role in the exaggerated bronchoconstrictor responses in many patients, however, an abnormality of the parasympathetic pathway cannot be the sole explanation for abnormal airway hyperresponsiveness.

Administration of the porphyrinogenic agent DDEP to PB-pretreated rats results in acute hepatic heme depletion, which is a characteristic of acute hepatic porphyria. Such acute heme depletion is associated with impaired hepatic tryptophan degradation and enhanced serotonergic tone in the CNS. We showed that intestinal motility in these rats is also significantly decreased, indicating that the serotonergic tone of the enteric nervous system may also be enhanced. In addition, the marked hepatic accumulation of glucogenic precursors, observed in parallel, indicates that the elevated tryptophan levels may also block hepatic glucogenesis. The clinical implications of these findings to acute heme-deficient states, such as the acute hepatic porphyrias, was discussed.