Kinin agonists

Kinin-B2 receptors, which are located in the jugular vein and carotid artery, respond to kinin agonists in the following order of potency ... 

POTENTIAL THERAPEUTIC USES Bradykinin contributes to many of the effects of the ACE inhibitors (Eigure 24-2). Aprotinin, a kallikrein inhibitor, is administered to patients undergoing coronary bypass to minimize bleeding and blood requirements (see below). Kinin agonists potentially may increase the delivery of chemotherapeutic agents past the blood-brain barrier. Based on some of the actions outlined earlier, kinin antagonists are being tested in inflammatory conditions. 

Tissue-specific Agonists/Antagonists Tissue-type Plasminogen Activator T-kinin (Ile-Ser-Bradykinin)... 

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. 

In contrast to the adverse physiologies associated with bradykinin release, there is a growing body of literature that implicates bradykinin as a protective agent during periods of cardiac or renal stress [14-16]. In this regard there is substantial evidence that the cardioprotective effects afforded by ACE-inhibitor treatment are a result of metabolically preserving bradykinin and are therefore mediated by bradykinin B2 (and possibly 1) receptors [17-18]. These results point to a possible therapeutic role for a kinin receptor agonist. 

There have been a variety of single alanine point mutations experimentally introduced into both rat and human bradykinin B2 receptors. Several of these have been shown to decrease the affinity of bradykinin to the receptor and have been implicated structurally near the agonist binding site. In contrast, at the time of this manuscript, there have been no mutations reported that adversely affect the ability of any peptide antagonists to bind to the receptor. Furthermore, antibodies raised against the certain extracellular domains of the kinin receptor compete with bradykinin for binding to the receptor but have no inhibitory... 

One final development worthy of note here is the development of novel anticancer agents that are dimeric bradykinin analogs. There has been a long-term interest in cross-linked kinin analogs as both agonists and antagonists of GPCRs... 

Thi ,DPhe BK [Thi ,DPhe ]-bradykinin. bradykinin-potentiating peptide teprotide. bradykinin potentiator B teprotide. BRADYKININ RECEPTOR AGONISTS act at sites recognizing members and derivatives of the bradykinin family of hormone peptides - kinins - of which bradykinin (BK) and kallidin (lysyl-bradykinin Lys-BK KD) are the main mammalian members. The bradykinin family is distinct from the tachykinin family of peptides, though both have profound hypotensive actions and contract many intestinal and other smooth muscles. Historically, it was noted that the former action was relatively slow-developing, hence the name bradykinin. Notable actions of bradykinin and kallidin are to dilate blood vessels and increase their permeability to plasma proteins, and to stimulate sensory nerve C-fibres. These actions are pro-inflammatory, and reflect the fact that the kinin-formation system is activated in inflammation, and enzymes (kallikreins) form the kinins from blood-borne or tissue precursors (kininogens) on injurious insult. 

Other natural mammalian kinins include T-kinin, [Hyp lBK and [Hyp JKD. Relatively few agonist ligands are used experimentally. These include at Bpreceptors BKi.i, KD1.9 and Sar[DPhe ]BKi.8 and at B2-receptors, there are BK.KD, [Hyp3,Tyr(Me) ]BK and [Phe ,itr(CH2-NH)-ArgSJBK. 

Following release, histamine binds to either HI or H2 histamine receptors causing a variety of effects (listed in Table 9.8). In addition to allergens, several other substances cause histamine release, including radiodiagnostic dyes, some antibiotics, kinins (chemicals released by immune cells) and some venoms. Several synthetic histamine agonists are available for laboratory studies of histamine functions, but there are virtually no clinical indications for histamine receptor agonists. 

KoUarik M, Undem BJ (2004) Activation of bronchopulmonary vagal afferent nerves with brady-kinin, acid and vanilloid receptor agonists in wild-type and TRPVl-/- mice. J Physiol (Lond) 555 115-123... 

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