Gap junction-dependent increases in smooth muscle cAMP underpin the EDHF phenomenon in rabbit arteries

Taylor, Hannah J., Chaytor, Andrew T., Edwards, David Hughes and Griffith, Tudor M. 2001. Gap junction-dependent increases in smooth muscle cAMP underpin the EDHF phenomenon in rabbit arteries. Biochemical and Biophysical Research Communications 283 (3) , pp. 583-589. 10.1006/bbrc.2001.4791

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Abstract

We have investigated the role of cAMP in nitric oxide (NO)- and prostanoid-independent vascular relaxations evoked by acetylcholine (ACh) in isolated arteries and perfused ear preparations from the rabbit. These EDHF-type responses are shown to be associated with elevated cAMP levels specifically in smooth muscle and are attenuated by blocking adenylyl cyclase or protein kinase A (PKA). Relaxations are amplified by 3-isobutyl-1-methylxanthine, which prevents cAMP hydrolysis, while remaining susceptible to inhibition by the combination of two KCa channel blockers, apamin and charybdotoxin. Analogous endothelium- and cAMP-dependent relaxations were evoked by cyclopiazonic acid (CPA) which stimulates Ca2+ influx via channels linked to the depletion of Ca2+ stores. Responses to ACh and CPA were both inhibited by interrupting cell-to-cell coupling via gap junctions with 18α-glycyrrhetinic acid and a connexin-specific Gap 27 peptide. The findings suggest that EDHF-type responses are initiated by capacitative Ca2+ influx into the endothelium and propagated by direct intercellular communication to effect relaxation via cAMP/PKA-dependent phosphorylation events in smooth muscle.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	endothelium-derived hyperpolarizing factor (EDHF); gap junctions; cyclic AMP; epoxyeicosatrienoic acids; cyclopiazonic acid
Publisher:	Elsevier
ISSN:	0006-291X
Last Modified:	04 Jun 2017 08:03
URI:	https://orca.cardiff.ac.uk/id/eprint/72318

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