Kinins and the Peripheral and Central Nervous Systems

Clark, William G.

doi:10.1007/978-3-642-67301-6_9

Cited by 32 publications

(18 citation statements)

References 141 publications

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“…The periaqueductal and periventricular grey regions were suggested as possible sites for this effect (Clark 1979;Couto et al 1995), and the release of endogenous opioids may account for the analgesia, as the bradykinin-mediated elevation of nociceptive thresholds was inhibited by intraperitoneal injections of naloxone (Burdin et al 1992). In the spinal cord, however, stimulation of descending noradrenergic nerve terminals has been implicated in the antinociceptive effect of kinins (Laneuville and Couture 1987;Laneuville et al 1989).…”

Section: Kinins and Central Painmentioning

confidence: 96%

Kinins and their receptors in hyperalgesia

Dray¹

1997

Can. J. Physiol. Pharmacol.

113

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Kinins (bradykinin, kallidin) are produced at sites of injury and inflammation and serve a critical role in signaling tissue distress as well as organising tissue responsiveness to injury. The acute activation and prolonged sensitization of fine afferents, to produce pain and hyperalgesia, are important in the protective responses that occur to minimize further tissue injury. These effects occur via activation of B2 receptors present on sensory neurons, resulting in a change of membrane excitability and altered cellular neurochemistry. B2 receptor activation of a variety of tissues including postganglionic sympathetic fibres stimulates the production of several proinflammatory mediators, including prostanoids and cytokines, which interact with kinins and contribute to inflammation and hyperalgesia. Increased expression of B1 receptors plays a prominent role in inflammatory hyperalgesia, but further characterization of the cellular mechanism is required. A role for kinins and kinin receptors in central pathophysiologies (trauma, ischemia, infection) needs examination. The evidence for modulation of nociception and central pain generation is compelling, as central bradykinin administration causes hyperalgesia, whereas B2 antagonists are antinociceptive. The basis for these effects should be urgently investigated. Such data will add further support to the utilization of bradykinin receptor antagonists for the treatment of peripheral and central pain.

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Section: Kinins and Central Painmentioning

confidence: 96%

Kinins and their receptors in hyperalgesia

Dray¹

1997

Can. J. Physiol. Pharmacol.

113

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“…There is evidence indicating that bradykinin may have a neuromodulator function in the mammalian central nervous system (Clark, 1979;Bhattacharya, Mohan Rao and Parmar, 1988). The kinin has been identified in the brains of several species, including rats, along with enzyme systems for synthesising and inactivating the kinin (Clark, 1979;Shisheva et al, 1983).…”

Section: Introductionmentioning

confidence: 97%

Anxiogenic activity of intraventricularly administered bradykinin in rats

1995

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The anxiogenic action of bradykinin was investigated in rats and compared with that of yohimbine, a known anxiogenic agent. Bradykinin (0.5, 1 and 2 μg/rat) was administered intracerebroventricularly (i.c.v.), whereas yohimbine (2 mg/kg) was administered i.p. The experimental methods used were the open- field, elevated plus-maze, social interaction and novelty suppressed feeding latency tests, and estimation of brain tribulin activity in terms of endogenous monoamine oxidase (MAO) A and MAO B inhibition. The behavioural and biochemical effects induced by bradykinin were qualitatively similar to those of yohimbine. Thus, both the drugs reduced ambulation and rears, and increased immobility and defecation, in the open-field test. They decreased the number of entries and time spent on the open arms of the elevated plus-maze, reduced social interaction in paired rats and increased the feeding latency in an unfamiliar environment in 48 h food-deprived rats. These effects are known to be associated with anxiety in animals. Bradykinin and yohimbine increased rat brain tribulin activity, the effect on the MAO A inhibitor component being more marked than that on the MAO B inhibitor component. The MAO A inhibitor component has been postulated to be the major anxiogenic moiety of tribulin. Lorazepam, a well known benzodiazepine anxiolytic agent, attenuated the anxiogenic effects of bradykinin and yohimbine, which may not be a functional effect. The investigation indicates that, like cholecystokinin (CCK), bradykinin may function as an endogenous anxiogenic peptide.

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“…It is possible, therefore, that under conditions such as exercise the kallikrein-kinin system may be activated as a result of enhanced sympathetic discharge to the heart, and in turn provide a reflexogenic stimulus for the cardiac sympathetic afferents that would amplify pressor response to exercise. This possibility is supported by reports of enhanced plasma kinin activity associated with strenuous exercise (Murakami, Hori & Masumura, 1968;Vecchiet, Dolce & Galleti, 1976) and a well-established ability of catecholamines (Castania & Rothschild, 1974) and sympathetic stimulation to activate a kallikrein-kinin system (Clark, 1979;Marin-Grez, 1982).…”

Section: Effects Of Epicardial Treatment By Aprotininmentioning

confidence: 79%

Participation of the kallikrein‐kinin‐receptor system in reflexes arising from neural afferents in the dog epicardium.

Staszewska-Woolley

Woolley

1989

The Journal of Physiology

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SUMMARY1. Reflexogenic effects of bradykinin, lysyl-bradykinin and endogenously formed kinins on neural afferents of the left ventricular epicardium were studied in anaesthetized, open-chest dogs.2. Epicardial application of either bradykinin (001-10 tg), lysyl-bradykinin (001-1O jug) or tissue kallikrein (0003-1 U) consistently resulted in dose-related increases in blood pressure and heart rate. The pressor and heart rate responses to epicardial kallikrein were slower in onset and longer lasting than those evoked by bradykinin or lysyl-bradykinin. The effects of kallikrein, but not those of exogenous kinins, were subject to tachyphylaxis. The application of higher doses of kallikrein (0 1 or 1 U) also resulted in long-lasting desensitization of the epicardium to the effects of bradykinin.3. Treatment of the epicardium with a proteinase inhibitor, aprotinin, prevented the reflexogenic effects of kallikrein but not those of bradykinin or lysyl-bradykinin. Treatment with aprotinin also counteracted post-kallikrein desensitization of sensory receptors of the ventricular epicardium to the reflexogenic effect of bradykinin.4. Superfusion of the epicardium with a selective B2 receptor antagonist, D-Arg[Hyp3,Thi5 8,D-Phe7]-bradykinin, was equally effective in antagonizing the reflexogenic effects of kallikrein, bradykinin and lysyl-bradykinin.5. We conclude that the response to epicardial application of kallikrein indicates an ample presence of endogenous substrate for local formation of bradykinin and/or related kinins. These then initiate reflex activation of the cardiovascular system by interacting with specific B2 receptors associated with sympathetic afferent neurones in the dog epicardium. We suggest that the kallikrein-kinin-receptor system has a role in the reflex functioA of the cardiac sympathetic afferents in both physiological and pathological conditions.

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Kinins and the Peripheral and Central Nervous Systems

Cited by 32 publications

References 141 publications

Kinins and their receptors in hyperalgesia

Kinins and their receptors in hyperalgesia

Anxiogenic activity of intraventricularly administered bradykinin in rats

Participation of the kallikrein‐kinin‐receptor system in reflexes arising from neural afferents in the dog epicardium.

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