Pre‐ and post‐junctional bradykinin B₂receptors regulate smooth muscle tension to the pig intravesical ureter

Abstract

Aims: Neuronal and non-neuronal bradykinin (BK) receptors regulate the contractility of the bladder urine outflow region. The current study investigates the role of BK receptors in the regulation of the smooth muscle contractility of the pig intravesical ureter. Methods: Western blot and immunohistochemistry were used to show the expression of BK B 1 and B 2 receptors and myographs for isometric force recordings. Results: B 2 receptor expression was consistently detected in the intravesical ureter urothelium and smooth muscle layer, B 1 expression was not detected where a strong B 2 immunoreactivity was observed within nerve fibers among smooth muscle bundles. On ureteral strips basal tone, BK induced concentration-dependent contractions, were potently reduced by extracellular Ca 2þ removal and by B 2 receptor and voltage-gated Ca 2þ (VOC) channel blockade. BK contraction did not change as a consequence of urothelium mechanical removal or cyclooxygenase and Rho-associated protein kinase inhibition. On 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F 2a (U46619)-precontracted samples, under non-adrenergic non-cholinergic (NANC) and nitric oxide (NO)-independent NANC conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B 2 receptor blockade. Kallidin, a B 1 receptor agonist, failed to increase preparation basal tension or to induce relaxation on U46619-induced tone. Conclusions: The present results suggest that BK produces contraction of pig intravesical ureter via smooth muscle B 2 receptors coupled to extracellular Ca 2þ entry mainly via VOC (L-type) channels. Facilitatory neuronal B 2 receptors modulating NO-dependent or independent NANC inhibitory neurotransmission are also demonstrated.

Signaling Pathways Mediating Bradykinin-Induced Contraction in Murine and Human Detrusor Muscle

“…However, it is noteworthy that the involvement of the Rho-ROCK pathway has also been demonstrated in BK-induced contractions of the vascular and the airway smooth muscles (47)(48)(49). On the other hand, Ribeiro et al reported recently that inhibition of ROCK by Y-27632 failed to alter the effect of BK in the pig intravesical ureter, indicating that not all BK-induced contractile effects in the lower urinary tract are sensitive to Y-27632 (3).…”

Signaling Pathways Mediating Bradykinin-Induced Contraction in Murine and Human Detrusor Muscle

“…However, it is noteworthy that the involvement of the Rho-ROCK pathway has also been demonstrated in BK-induced contractions of the vascular and the airway smooth muscles (47)(48)(49). On the other hand, Ribeiro et al reported recently that inhibition of ROCK by Y-27632 failed to alter the effect of BK in the pig intravesical ureter, indicating that not all BK-induced contractile effects in the lower urinary tract are sensitive to Y-27632 (3).…”

Does this case hold the answer to one of the worse types of pain in medicine—that of loin pain haematuria syndrome (LPHS)

“…The coagulation status of blood in the haematuria is unknown, however, clots have been reported 2 3. If the coagulation cascade is activated, with or without clot disruption, the activation of the complement and plasma protein cascades as well as platelets would release potent mediators such as C3a, C5a, kinins and thromboxane, for which the ureter possesses receptors, and may contract chronically in response 8 9. Indeed, it may be hypothesised that these factors may synergise to produce a tetanic state.…”

Regulation of the lower urinary tract: urination and urinary incontinence

“…Diversos estudios han demostrado que el NO, la adenosina, el NPY, el VIP, el CGRP, la 5HT, el H 2 S y las taquicininas están involucrados en la neurotransmisión de la unión uréterovesical (36,37,38,39,40). El NO y el CGRP participan en la neurotransmisión inhibitoria ureteral relajando el músculo liso a través de un mecanismo dependiente del GMPc y del AMPc, respectivamente, mediante la activación de canales de K + sensibles a la glibenclamida.…”

Signaling Pathways Mediating Bradykinin-Induced Contraction in Murine and Human Detrusor Muscle

“…However, it is noteworthy that the involvement of the Rho-ROCK pathway has also been demonstrated in BK-induced contractions of the vascular and the airway smooth muscles (47)(48)(49). On the other hand, Ribeiro et al reported recently that inhibition of ROCK by Y-27632 failed to alter the effect of BK in the pig intravesical ureter, indicating that not all BK-induced contractile effects in the lower urinary tract are sensitive to Y-27632 (3).…”

Does this case hold the answer to one of the worse types of pain in medicine—that of loin pain haematuria syndrome (LPHS)

“…The coagulation status of blood in the haematuria is unknown, however, clots have been reported 2 3. If the coagulation cascade is activated, with or without clot disruption, the activation of the complement and plasma protein cascades as well as platelets would release potent mediators such as C3a, C5a, kinins and thromboxane, for which the ureter possesses receptors, and may contract chronically in response 8 9. Indeed, it may be hypothesised that these factors may synergise to produce a tetanic state.…”

Regulation of the lower urinary tract: urination and urinary incontinence

“…Diversos estudios han demostrado que el NO, la adenosina, el NPY, el VIP, el CGRP, la 5HT, el H 2 S y las taquicininas están involucrados en la neurotransmisión de la unión uréterovesical (36,37,38,39,40). El NO y el CGRP participan en la neurotransmisión inhibitoria ureteral relajando el músculo liso a través de un mecanismo dependiente del GMPc y del AMPc, respectivamente, mediante la activación de canales de K + sensibles a la glibenclamida.…”

Signaling Pathways Mediating Bradykinin-Induced Contraction in Murine and Human Detrusor Muscle

“…However, it is noteworthy that the involvement of the Rho-ROCK pathway has also been demonstrated in BK-induced contractions of the vascular and the airway smooth muscles (47)(48)(49). On the other hand, Ribeiro et al reported recently that inhibition of ROCK by Y-27632 failed to alter the effect of BK in the pig intravesical ureter, indicating that not all BK-induced contractile effects in the lower urinary tract are sensitive to Y-27632 (3).…”

Does this case hold the answer to one of the worse types of pain in medicine—that of loin pain haematuria syndrome (LPHS)

“…The coagulation status of blood in the haematuria is unknown, however, clots have been reported 2 3. If the coagulation cascade is activated, with or without clot disruption, the activation of the complement and plasma protein cascades as well as platelets would release potent mediators such as C3a, C5a, kinins and thromboxane, for which the ureter possesses receptors, and may contract chronically in response 8 9. Indeed, it may be hypothesised that these factors may synergise to produce a tetanic state.…”

Regulation of the lower urinary tract: urination and urinary incontinence

“…Diversos estudios han demostrado que el NO, la adenosina, el NPY, el VIP, el CGRP, la 5HT, el H 2 S y las taquicininas están involucrados en la neurotransmisión de la unión uréterovesical (36,37,38,39,40). El NO y el CGRP participan en la neurotransmisión inhibitoria ureteral relajando el músculo liso a través de un mecanismo dependiente del GMPc y del AMPc, respectivamente, mediante la activación de canales de K + sensibles a la glibenclamida.…”