KININS AND KININ RECEPTORS IN THE NERVOUS-SYSTEM

Kinins, including bradykinin and kallidin, are peptides that are produ ced and act at the site of tissue injury or inflammation. They induce a variety of effects via the activation of specific B-1 or B-2 recepto rs that are coupled to a number of biochemical transduction mechanisms . In the periphery the actions of kinins include vasodilatation, incre ased vascular permeability and the stimulation of immune cells and pep tide-containing sensory neurones to induce pain and a number of neurop eptide-induced reflexes. Mechanisms for kinin synthesis are also prese nt in the CNS where kinins are likely to initiate a similar cascade of events, including an increase in blood flow and plasma leakage. Kinin s are potent stimulators of neural and neuroglial tissues to induce th e synthesis and release of other pro-inflammatory mediators such as pr ostanoids and cytotoxins (cytokines, free radicals, nitric oxide). The se events lead to neural tissue damage as well as long lasting disturb ance sin blood-brain barrier function. Animal models for CNS trauma an d ischaemia show that increases in kinin activity can be reversed eith er by kinin receptor antagonists or by the inhibition of kinin product ion. A number of other central actions have been attributed to kinins including an effect on pain signalling, both within the brain (which m ay be related to vascular headache) and within the spinal dorsal horn where primary afferent nociceptors can be stimulated. Kinins also appe ar to play a role in cardiovascular regulation especially during chron ic spontaneous hypertension. Presently, however, direct evidence is la cking for the release of kinins in pathophysiological conditions of th e CNS and it is not known whether spinal or central neurones, other th an afferent nerve terminals, are sensitive to kinins. A more detailed examination of the effects of kinins and their central pharmacology is necessary. It is also important to determine whether the inhibition o f kinin activity will alleviate CNS inflammation and whether kinin rec eptor antagonists are useful in pathological conditions of the CNS.