B<sub>1</sub> bradykinin receptors and sensory neurones

Davis, Clare; Naeem, Sami; Phagoo, Steve B.; Campbell, Elizabeth A.; Urbán, László; Burgess, Gillian M.

doi:10.1111/j.1476-5381.1996.tb15562.x

Cited by 62 publications

(26 citation statements)

References 55 publications

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“…In the present study, we have shown that the size of this component is selectively facilitated in the presence of des-Arg 9 -BK, a specific agonist of the B1 receptor. Unlike neurokinin-receptor activation (36), des-Arg 9 -BK did not directly depolarize the ventral root when applied in vitro (37). The facilitation, which recovered within 20 min after washout of des-Arg 9 -BK, was not observed in isolated spinal cords obtained from B1-receptor knockout mice.…”

Section: Discussionmentioning

confidence: 88%

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Pesquero

Araújo

Heppenstall

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

344

259

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Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. Two kinin receptors have been described, B1 and B2. The B2 receptor is constitutively expressed, and its targeted disruption leads to salt-sensitive hypertension and altered nociception. The B1 receptor is a heptahelical receptor distinct from the B2 receptor in that it is highly inducible by inflammatory mediators such as bacterial lipopolysaccharide and interleukins. To clarify its physiological function, we have generated mice with a targeted deletion of the gene for the B1 receptor. B1 receptor-deficient animals are healthy, fertile, and normotensive. In these mice, bacterial lipopolysaccharide-induced hypotension is blunted, and there is a reduced accumulation of polymorphonuclear leukocytes in inflamed tissue. Moreover, under normal noninflamed conditions, they are analgesic in behavioral tests of chemical and thermal nociception. Using whole-cell patch-clamp recordings, we show that the B1 receptor was not necessary for regulating the noxious heat sensitivity of isolated nociceptors. However, by using an in vitro preparation, we could show that functional B1 receptors are present in the spinal cord, and their activation can facilitate a nociceptive reflex. Furthermore, in B1 receptor-deficient mice, we observed a reduction in the activitydependent facilitation (wind-up) of a nociceptive spinal reflex. Thus, the kinin B1 receptor plays an essential physiological role in the initiation of inflammatory responses and the modulation of spinal cord plasticity that underlies the central component of pain. The B1 receptor therefore represents a useful pharmacological target especially for the treatment of inflammatory disorders and pain.D iseases of the cardiovascular system as well as inflammatory diseases that often lead to pain are of increasing importance for health care in aging populations. Kinins have been known for some time to be important mediators of cardiovascular homeostasis, inflammation, and nociception (1). They are probably the first mediators released in injured tissue from kininogens either by plasma kallikrein, which is activated early in the coagulation cascade, or tissue kallikrein, which is activated by proteases released at injured sites. Surprisingly, the therapeutic value of intervention in the kallikrein-kinin system has not been fully explored. The two known receptors for kinins, B1 and B2, might be suitable pharmacological targets to treat chronic inflammatory and cardiovascular diseases. The B2 receptor binds the major effector peptide of the kallikrein-kinin system, which is bradykinin (BK) in rodents and kallidin in humans. Deletion of the B2 receptor in mice leads to salt-sensitive hypertension and altered nociception (2-4). Like the B2 receptor, the B1 receptor is a heptahelical receptor, but unlike B2 receptors, it is not widely expressed in normal tissue but is highly inducible by inflammatory mediators like bacterial lipopolysaccharide (LPS) and cytokines and does not desensitize after...

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Section: Discussionmentioning

confidence: 88%

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Pesquero

Araújo

Heppenstall

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

344

259

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“…Activation of bradykinin B 2 receptors on sensory nerves produces pain and hyperalgesia by depolarization and sensitization of nerve fibers to physical stimuli (heat and mechanical), whereas activation of B 2 receptors on other tissues such as sympathetic nerves and inflammatory cells stimulates the production of proinflammatory mediators such as prostanoids and cytokines (Dray, 1997). The B 1 receptor, for which the major metabolite of bradykinin des-Arg 9 -bradykinin has a greater affinity than the parent peptide, is expressed under inflammatory conditions and plays a prominent role in inflammatory hyperalgesia by actions on targets other than sensory nerves (Dray and Perkins, 1993;Davis et al, 1996). The involvement of both B 1 and B 2 receptors in inflammatory hyperalgesia suggests that kinin antagonists might be useful analgesics in such conditons.…”

Section: Antagonists For Inflammatory Mediatorsmentioning

confidence: 99%

Topical and Peripherally Acting Analgesics

2003

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“…Most of these cells effects are connected with the activation of B 2 receptors, since only these receptors were found to be located on nociceptive neurons [6,7]. However, more recently, it has been found that activation of B 1 receptors, located on other than sensory cells, may be responsible for the release of mediators sensitizing or activating nociceptors [8]. Furthermore, the existence of B 1 receptors on dorsal horn neurons in the spinal cord as well as on bipolar neurons of the dorsal root ganglia was also demonstrated [9].…”

Section: Introductionmentioning

confidence: 99%

Intrathecal Bradykinin Administration: Opposite Effects on Nociceptive Transmission

Sot

Misterek²,

Gumulka³

et al. 2002

Pharmacology

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Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15 µg) or antinociception (6.0 µg) in rats when thermal noxious stimuli were used. Similarly, des-Arg⁹-BK at the lower dose (0.15 µg) decreased, whereas at the higher dose (6.0 µg) it increased the threshold to thermal noxious stimuli; however, these effects were less pronounced than those of BK. The antinociception induced by BK was abolished by HOE 140, a B₂ receptor antagonist, injected intrathecally at a dose of 1.3 ng and was markedly attenuated by des-Arg¹⁰-HOE 140, a B₁ receptor antagonist (1.15 ng i.t.). The results obtained in this study showed that – depending on the dose used – BK and des-Arg⁹-BK could produce pro- as well as antinociceptive actions. Both B₂ and B₁ receptors are involved in the action of intrathecally applied BK.

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B₁ bradykinin receptors and sensory neurones

Cited by 62 publications

References 55 publications

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Topical and Peripherally Acting Analgesics

Intrathecal Bradykinin Administration: Opposite Effects on Nociceptive Transmission

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B1 bradykinin receptors and sensory neurones

Cited by 62 publications

References 55 publications

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Topical and Peripherally Acting Analgesics

Intrathecal Bradykinin Administration: Opposite Effects on Nociceptive Transmission

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Product

Resources

About

B₁ bradykinin receptors and sensory neurones