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Title: Mechanisms by which the 5-hydroxytryptamine 1B (5-HT1B) receptor inhibits isoprenaline-induced vasodilation of bovine pulmonary arteries
Author: Maghoud, Hwuida K. H. Abdelhafid
Awarding Body: Glasgow Caledonian University
Current Institution: Glasgow Caledonian University
Date of Award: 2014
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Recently the 5-hydroxytryptamine 1B (5-HTIB) receptor has been shown to inhibit vasodilation in bovine pulmonary arteries (BP A) mediated by a range of vasodilators including the B-adrenoceptor agonist isoprenaline and the type 4 phosphodiesterase (PDE4) inhibitor rolipram (McKenzie et al., 2010). This study has concentrated on investigating the mechanism(s) by which isoprenaline, and for comparison rolipram, induces vasodilation of in vitro preparations of BP A and the mechanism(s) by which the 5-HTIB receptor inhibits vasodilation. This work finds that the 5-HTIB receptor contributes to the 5-HT-induced contraction by stimulating the reverse mode of the sodium:calcium exchanger (NCX). An increase in local [Na +]i mediated by sodium:hydrogen exchanger (NHX) is also required to drive the reverse mode of NCX. Isoprenaline and rolipram can induce full relaxation of BP A contracted with histamine and U46619 but only partial relaxation (approximately 50%) of 5-HT-constricted BPA. Both Bland B2-adrenoceptors appear to contribute to the isoprenaline-induced relaxation. The ability of the 5-HTIB receptor to inhibit isoprenaline-mediated relaxation is not associated with inhibition of particular receptor. The present study suggests that isoprenaline- and rolipraminduced relaxation of BP A may be composed of two components. For isoprenaline the first component (approx. 50%) is associated with activation of Na:K ATPase (NKA) and large conductance calcium-activated potassium channel (BKca), possibly mediating relaxation through membrane hyperpolarization, whereas for rolipram this component is associated with activation of adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA). For both agents the second component of relaxation (approx. 50%) is mediated by stimulation of the forward mode ofNCX mediating relaxation through Ca2+ extrusion. Therefore 5-HTIB receptor stimulation of the NCX reverse mode may oppose the isoprenaline- or rolipram-induced stimulation of the forward mode of NCX to prevent this element of the relaxation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available