B2 receptor

BK actions are mediated through at least two types of GPCR B and B2. At the B receptor, des-Arg BK is more potent than BK. The converse is tme at the B2 receptor. The effects of BK are primarily mediated by activation of the B2 receptor because the B receptor has limited tissue distribution and is iaduced by noxious stimuli such as apamin or an inflammatory mediator-type response. The existence of a B receptor was suggested on the basis of limited efficacy of known antagonists ia some systems. A B receptor may also exist. The human B2 receptor has been cloned. 

Bradykinin is also released from mast cells within damaged tissues. It produces inflammation and activates nociceptors via bradykinin B1 and B2 receptors. 

H-kininogen Plasma kallikrein bradykinin (RPPGFSPFR) B2 receptor... 

Mice that are homozygous for a disrupted Bx or B2 receptor gene are healthy, fertile and normotensive. In Bx-deficient mice, bacterial lipopolysaccharide-induced hypotension is diminished and the recruitment of polymorphonuclear leukocytes to the sites of tissue injury is impaired, and the animals show signs of hypoalgesia. Deletion of the B2 gene in mice leads to salt-sensitive hypertension and altered nociception. 

ACE not only activates angiotensin but is also involved in the metabolism of other peptides, e.g., it is a major kinin-degrading enzyme. Therefore, ACE inhibitors also increase kinin concentrations. Furthermore, it has recently been shown that these drugs potentiate kinin effects by modulating a direct interaction between the ACE protein and the kinin B2 receptor, which is independent from the enzymatic activity of ACE. Kinin potentiation may be involved in the beneficial action of ACE inhibition since kinins are known to exert cardio- and renoprotective actions. 

Davis A, Perkins M The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat. Br J Pharmacol 1994 113 63-68. 

Bas M. Bier H. Greve J, Kojda G, Hoffmann T Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. Allergy 2006 61 1490-1492. 

Bki, Bk2 receptors Bradykinin receptor subtypes also known as B and B2 receptors... 

Contribution of bradykinin B2 receptor dysfunction to abnormal coronary vaso-motion in humans. J Am Coll Cardiol 2000 36 1467-1473. 

Pizard, A., Marchetti, J., Allegrini, J., Alhenc-Gelas, F., and Rajerison, R. M. (1998) Negative cooperativity in the human bradykinin B2 receptor. J. Biol. Chem. 273, 1309-1315. 

Our final peptidomimetic example is compound FR190997 (6.119), a mimic of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, see also Fig. 6.34) that has high affinity and selectivity for the human B2 receptor. Remarkably and in contrast to many analogues, FR190997 is a bradykinin... 

Like angiotensin 11, non-peptide B2 receptor antagonists and agonists of bradykinin were obtained by random screening approaches. Chemical modifications on random screening leads like 101 led to non-peptide antagonists... 

Meini S, Cucchi P, BeUucci F, et al. Site-directed mutagenesis at the human B2 receptor and molecular modelling to define the pharmacophore of non-peptide bradykinin receptor antagonists. Biochem Pharmacol 2004 67 601-9. 

Sawada Y, Kayakiri H, Abe Y, et al. A new class of nonpeptide bradykinin B2 receptor ligands, incorporating a 4-aminoquinoline framework. Identification of a key pharmacophore to determine species difference and agonist/antagonist profile. 7 Med Chem 2004 47 2667-77. 

Bradykinin exerts its physiological effects via two receptors, the B1 and B2 receptors, with most of its physiological effects being mediated by the B2 receptor. The precise function of the B1 receptor is unclear however, some of the chronic inflammatory responses to bradykinin may be mediated through actions at this receptor. 

Bradykinin antagonists of the B2 receptor are currently in development and may find utility in the treatment of pain associated with burns and such chronic inflammatory disorders as arthritis, asthma, and chronic pain. 

A predominance of norepinephrine b -receptors in the CNS and of norepinephrine b2-receptors in peripheral tissues... 

Receptor desensitization may also be mediated by second-messenger feedback. For example, adrenoceptors stimulate cAMP accumulation, which leads to activation of protein kinase A protein kinase A can phosphorylate residues on receptors, resulting in inhibition of receptor function. For the B2 receptor, phosphorylation occurs on serine residues both in the third cytoplasmic loop and in the carboxyl terminal tail of the receptor. Similarly, activation of protein kinase C by Gq-coupled receptors may lead to phosphorylation of this class of G protein-coupled receptors. This second-messenger feedback mechanism has been termed heterologous desensitization because activated protein kinase A or protein kinase C may phosphorylate any structurally similar receptor with the appropriate consensus sites for phosphorylation by these enzymes. 

The rise in systolic blood pressure that occurs after epinephrine release or administration is caused by its positive inotropic and chronotropic actions on the heart (predominantly Bj receptors) and the vasoconstriction induced in many vascular beds (a receptors). Epinephrine also activates B2 receptors in some vessels (eg, skeletal muscle blood vessels), leading to their dilation. Consequently, total peripheral resistance may actually fall, explaining the fall in diastolic pressure that is sometimes seen with epinephrine injection (Figure... 

The AT2 receptor has a structure and affinity for Ang II similar to those of the A receptor. In contrast, however, stimulation of AT2 receptors causes vasodilation that may serve to counteract the vasoconstriction resulting from ATi receptor stimulation. AT2 receptor-mediated vasodilation appears to be nitric oxide (NO)-dependent and may involve the bradykinin B2 receptor-NO-cGMP pathway. 

The biologic actions of kinins are mediated by specific receptors located on the membranes of the target tissues. Two types of kinin receptors, termed Bj and B2, have been defined based on the rank orders of agonist potencies. (Note that here stands for bradykinin, not for -adrenoceptor.) Bradykinin displays the highest affinity in most B2 receptor systems, followed by lys-bradykinin and then by met-lys-bradykinin. One exception is the B2 receptor that mediates contraction of venous smooth muscle this appears to be most sensitive to lys-bradykinin. Recent evidence suggests the existence of two B2-receptor subtypes, which have been termed B2A and B2B. 

Drugs that modify the activity of the kallikrein-kinin system are available, though none are in wide clinical use. Considerable effort has been directed toward developing kinin receptor antagonists, since such drugs have considerable therapeutic potential as anti-inflammatory and antinociceptive agents. Competitive antagonists of both and B2 receptors are available for research use. Examples of B receptor... 

---