KININS AND RESPIRATORY-TRACT DISEASES

Bradykinin and related kinins are peptidic hormones, formed in tissues and fluids during inflammation. Various functional sites have been pr oposed as mediators of the biological effects of kinins, including the B1, B2 and B3 receptors. The existence of the B1 and the B2 receptor has largely been confirmed, whilst that of the B3 receptor is controve rsial and needs further confirmation. The role of bradykinin in the pa thophysiology of asthma is not well understood, but bradykinin was pro posed as a putative mediator of asthma, since asthmatic subjects are h yperresponsive to bradykinin, and since immunoreactive kinins are incr eased in the bronchoalveolar lavage fluids of asthmatic patients. Kini ns could provoke bronchoconstriction by acting directly on smooth musc le and/or indirectly by their inflammatory properties. They may also c ontribute to the symptomatology of allergic and viral rhinitis, since they are the only mediators detected to date that are generated in nas al secretion during experimental and natural rhinovirus colds. Moreove r, they can induce relevant symptoms when applied to airway mucosa. It has also been proposed that coughing during treatment with angiotensi n-converting enzyme (ACE) inhibitors is linked to the action of kinins , since ACE is able to degrade kinins, and since the effects of ACE in hibitors are reduced by kinin antagonists. Due to their mitogenic prop erties, kinins have been proposed to regulate lung carcinoma growth. T heir action remains speculative, but some findings are of great intere st in order to define their role in these pathologies. Despite many st udies in animals and in humans, the mode of action of kinins in airway s is still poorly understood. The recent cloning and sequencing of the complementary deoxyribonucleic acid (cDNA) of a human B2 receptor, an d the availability of selective B2 antagonists will be useful for defi ning more precisely the action of kinins on airways functions.