• Journal of Integrative Natural Science
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• v.10 no.2
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• pp.74-77
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• 2017

Bradykinin receptor B2 (B2R) is a GPCR protein which binds with the inflammatory mediator hormone bradkynin. Kallidin, a decapeptide, also signals through this receptor. B2R is crucial in the cross-talk between renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS) and in many processes including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Thus the structural study of the receptor becomes important. We have predicted the peptide structures of Bradykinin and Kallidin from their amino acid sequences and the structures were docked with the receptor structure. The results obtained from protein-protein docking could be helpful in studying the B2R structural features and in the pathophysiology in various diseases related to it.

• Journal of Integrative Natural Science
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• v.9 no.4
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• pp.234-240
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• 2016

Bradykinin receptor B2, a GPCR protein, binds with the inflammatory mediator hormone bradkynin. It plays an important role in cross-talk between the renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS). Also, it is involved in many processes including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Hence, studuying the structural features of the receptor becomes important. But the unavailability of the three dimensional structure of the protein makes the analysis difficult. Hence we have performed the homology modelling of Bradykinin receptor B2 with 5 different templates. 25 different homology models were constructed. Two best models were selected based on the model validation. The developed models could be helpful in analysing the structural features of Bradykinin receptor B2 and in pathophysiology of various disorders related to them.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.233-241
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• 1995

The nonapeptide bradykinin has been shown to exhibit an array of biological activities including relaxation/contraction of various smooth muscles. In order to investigate the effects of bradykinin on the contractility and the electrical activity of antral circular muscle of guinea-pig stomach, the isometric contraction and membrane potential were recorded. Also, using standard patch clamp technique, the $Ca^{2+}-activated$ K currents were recorded to observe the change in cytosolic $Ca^{2+}$ concentration. $0.4 {\mu}M$ bradykinin induced a triphasic contractile response (transient contraction-transient relaxation-sustained contraction) and this response was unaffected by pretreatment with neural blockers (tetrodotoxin, atropine and guanethidine) or with apamin. Bradykinin induced hyperpolarization of resting membrane potential and enhanced the amplitude of slow waves and spike potentials. The enhancement of spike potentials was blocked by neural blockers. Both the bradykinin-induced contractions and changes in membrane potential were reversed by the selective $B_2$-receptor antagonist $(N{\alpha}-adamantaneacetyl-_{D}-Arg-[Hyp, Thy,_{D}-Phe]-bradykinin)$. In whole-cell patch clamp experiment, we held the membrane potential at -20 mV and spontaneous and transient changes of Ca-activated K currents were recorded. Bradykinin induced a large transient outward current, consistent with a calcium-releasing action of bradykinin front the intracellular calcium pool, because such change was blocked by pretreatment with caffeine. Bradykinin-induced contraction was also blocked by pretreatment with caffeine. From these results, it is suggested that bradykinin induces a calciumrelease and contraction through the $B_{2}$ receptor of guinea-pig gastric smooth muscle. Enhancement of slow wave activity is an indirect action of bradykinin through enteric nerve cells embedded in muscle strip.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.4
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• pp.231-238
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• 2003

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin $(3{\times}10^{-8}M)$ alone produced a weak secretory response of the CA. however, the perfusion with bradykinin $(3{\times}10^{-8}M)$ into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}M)$, excess $K^+$ ($5.6{\times}10^{-2}M$, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic agonist) and McN-A-343 ($10^{-4}$ M, a selective M1-muscarinic agonist). Moreover, bradykinin ($3{\times}10^{-8}$ M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels. However, in the presence of $(N-Methyl-D-Phe^7)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_2$-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys-$(des-Arg^9,\;Leu^9)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_1$-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin $(3{\times}10^{-6}M)$ into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess $K^+$ $(5.6{\times}10^{-2}M)$. Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of $B_2$-bradykinin receptors, not through $B_1$-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased $Ca^{2+}$ influx through the activation of the dihydropyridine L-type $Ca^{2+}$ channels.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.192.1-192.1
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• 2003

Histamine is found in most tissues of the body and activates polymodal nociceptors via unmyelinated afferent C-fibres. We have demonstrated that bradykinin. acting at B2 bradykinin receptors. excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid in dorsal root ganglion. Histamine is known to the activator of phospholipase A2- arachidonic acid pathway via a G-protein- coupled H1 receptor. (omitted)

• Journal of Veterinary Science
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• v.24 no.2
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• pp.26.1-26.11
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• 2023

Background: Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. Objectives: This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. Methods: Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. Results: The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme. In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B1 receptor antagonist, R 715, or the BK B₂ receptor antagonist, HOE 140. Conclusions: These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.

• Proceedings of the Korean Biophysical Society Conference
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• 1998.06a
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• pp.32-32
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• 1998

The effect of neurotensin (NT) was investigated in rat pheochromocytoma (PC12) cells. When PC12 cells were treated with micromolar concentrations of NT, [$^3$H]norepinephrine ([$^3$H]NE) secretion and elevation of cytosolic Ca$\^$2＋/ concentration ([Ca$\^$2＋/]i) were evoked in a concentration-dependent manner with an EC$\sub$50/ of 50 ${\mu}$M.(omitted)