Effects of Bradykinin on Calcium signalling and contractility of ureter

Alfituri, AM ORCID: 0000-0002-5172-1321 (2017) Effects of Bradykinin on Calcium signalling and contractility of ureter. PhD thesis, University of Liverpool.

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Abstract

The understanding of the mechanism, by which bradykinin (BK) effects ureteric contractility, is limited. The primary aim of this study was to determine the expression and the distribution of B2 receptors along the length of the ureter and study the effects of BK on Ca2+ signalling and contractile activity of the rat ureteric smooth muscle. Both the Ca2+-dependent and Ca2+-independent pathways, underlying the stimulant action of BK on the ureteric smooth muscle, have been investigated. Immunohistochemistry was used to identify the presence and the distribution of B2 receptors along the ureter. Confocal imaging combined with force measurements under different physiological conditions was used to study the effects of BK on Ca2+ signalling and force of the ureteric smooth muscle in situ. The effect of the selective blocker of Rho-associated kinase, Y-27632, on force/ Ca2+ relationship was investigated. It was found that the distribution of the B2 receptors is non-homologous along the length of the rat ureter, with the expression being greater in the upper ureter and lowest in the middle and the lower ureter. It was found that BK caused a complex contractile response, consisting of an initial phasic component, associated with the Ca2+ release from the store, which appeared as asynchronous Ca2+ waves, followed by a sustained component, associated with Ca2+ entry via store/receptor operated Ca2+ channels that was superimposed by multiple phasic contractions, associated with propagating intercellular Ca2+ waves. The L-type Ca2+ channel blocker, Nifedipine, selectively blocked the intercellular Ca2+ wave and the repeated phasic contraction, but had no effect on the initial phasic contraction, associated with the Ca2+ release from the sarcoplasmic reticulum. Nifedipine, also had no effect on the sustained slow component, associated with the Ca2+ entry via store/receptor operated Ca2+ channels. Y-27632 had no effects on the Ca2+ signalling, associated with the Ca2+ release from the store or the Ca2+ entry via store/receptor operated Ca2+ channels, but had significant inhibitory effects on the initial phasic and sustained tonic component of BK-induced contractile response. There was a significant reduction in the amplitude and an increase in the rate of relaxation of the initial phasic component, suggesting an increase of the activity of myosin light chain phosphatase, responsible for dephosphorylation of MLC20 and relaxation of force in the smooth muscles. Collectively, the data obtained indicate that both Ca2+-dependent and Ca2+-independent mechanisms are involved in BK-induced stimulant action on the rat ureteric smooth muscle.

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health and Life Sciences > Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	19 Dec 2017 10:27
Last Modified:	19 Jan 2023 06:51
DOI:	10.17638/03011383
Supervisors:	Burdyga, T Varro, A
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3011383