Pathophysiology of the kallikrein-kinin system in mammalian nervous tissue.
The nervous system and peripheral tissues in mammals contain a large number of biologically active peptides and proteases that function as neurotransmitters or neuromodulators in the nervous system, as hormones or cellular mediators in peripheral tissue, and play a role in human neurological diseases. The existence and possible functional relevance of bradykinin and kallidin (the peptides), kallikreins (the proteolytic enzymes), and kininases (the peptidases) in neurophysiology and neuropathological states are discussed in this review. Tissue kallikrein, the major cellular kinin-generating enzyme, has been localised in various areas of the mammalian brain. Functionally, it may assist also in the normal turnover of brain proteins and the processing of peptide-hormones, neurotransmitters, and some of the nerve growth factors that are essential for normal neuronal function and synaptic transmission. A specific class of kininases, peptidases responsible for the rapid degradation of kinins, is considered to be identical to enkephalinase A. Additionally, kinins are known to mediate inflammation, a cardinal feature of which is pain, and the clearest evidence for a primary neuronal role exists so far in the activation by kinins of peripherally located nociceptive receptors on C-fibre terminals that transmit and modulate pain perception. Kinins are also important in vascular homeostasis, the release of excitatory amino acid neurotransmitters, and the modulation of cerebral cellular immunity. The two kinin receptors, B2 and B1, that modulate the cellular actions of kinins have been demonstrated in animal neural tissue, neural cells in culture, and various areas of the human brain. Their localisation in glial tissue and neural centres, important in the regulation of cardiovascular homeostasis and nociception, suggests that the kinin system may play a functional role in the nervous system.
Raidoo
D M
DM
Department of Physiology, Faculty of Medicine, University of Natal, Durban, South Africa.
Bhoola
K D
KD
D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000502:physiology; D001932:Brain Neoplasms / Q000503:physiopathology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D051381:Rats