CENTRAL TACHYKININS - MEDIATORS OF DEFENSE REACTION AND STRESS REACTIONS

The tachykinins substance P, neurokinin A, and neurokinin B are natura l agonists for NK1, NK2, and NK3 receptors, respectively. Evidence fro m biochemical, neurophysiological, pharmacological, and molecular biol ogy studies indicates that the tachykinin-containing pathways within t he brain contribute to central cardiovascular and endocrine regulation and to the control of motor activity. The hypothalamus, which represe nts a site for the integration of central neuroendocrine and autonomic processes, is rich in tachykinin nerve endings and tachykinin recepto rs. Stimulation of periventricular or hypothalamic NK1 receptors in co nscious rats induces an integrated cardiovascular, behavioural, and en docrine response. The cardiovascular response is associated with incre ased sympathoadrenal activity and comprises an increase in blood press ure and heart rate, mesenteric and renal vasoconstriction, and hind-li mb vasodilatation. The behavioural response consists of increased loco motion and grooming behaviour. This response pattern is consistent wit h an integrated stress response to nociceptive stimuli and pain in rod ents. Several studies have demonstrated rapid changes in substance P l evels and its receptors in distinct brain areas following acute stress . These data indicate that substance P and other tachykinins, in addit ion to serving as nociceptive and pain transmitters in the spinal cord , may act in the brain as neurotransmitters - neuromodulators within t he neuronal circuits mediating central stress responses.