ABSTRACT
The postpericardiotomy syndrome may occur as a complication of temporary and permanent pacing. Physicians involved in procedures which may be complicated by this condition therefore need to be aware of its diagnosis and management.
Subject(s)
Cardiac Pacing, Artificial/adverse effects , Postpericardiotomy Syndrome/etiology , Aged , Autoimmunity , Echocardiography , Humans , Male , Postpericardiotomy Syndrome/diagnosis , Postpericardiotomy Syndrome/therapyABSTRACT
Previous work has shown that truncating the carboxyl terminus (C-terminus) of the rat angiotensin AT1A receptor to 309 amino acids abolished G-protein coupling and receptor internalization. This suggests that domains responsible for these functions lie beyond amino acid 309 of the C-terminus. The objective of this study was to determine the effect on angiotensin AT1A receptor function and regulation of deleting 41 amino acids from the C-terminus, which include the putative protein kinase C phosphorylation sites. Using site directed mutagenesis, the codon for Tyr319 was converted to a stop codon and the resulting truncated receptor permanently expressed in cultured human kidney cells. The properties of the truncated receptor were compared to those of the full length receptor. Expression of the truncated receptor was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis of photolabelled membrane preparations. Angiotensin II activation of both full length and truncated receptors resulted in mobilization of inositol phosphates. However, whereas this was associated with rapid internalization of the full length receptor, the truncated receptor failed to internalize. Furthermore, pretreatment of cells with phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, markedly attenuated the full length, but no the truncated receptor's ability to mobilise inositol phosphates. Thus, we conclude that the domain between amino acids 309 & 318 is important for G-protein coupling; that amino acids beyond 318 regulate internalization and one or more of the putative protein kinase C phosphorylation sites, present in the C-terminus of the angiotensin At1A receptor, actively regulate the receptor.
Subject(s)
Angiotensin II/pharmacology , Kidney/drug effects , Receptors, Angiotensin/drug effects , Receptors, Angiotensin/physiology , Animals , Base Sequence , Binding, Competitive , Dose-Response Relationship, Drug , Humans , Molecular Sequence Data , Radioligand Assay , Rats , Time FactorsSubject(s)
Angiotensin II/analogs & derivatives , Angiotensin II/metabolism , Angiotensin I/metabolism , Azides/metabolism , Receptors, Angiotensin/chemistry , Receptors, Angiotensin/metabolism , Affinity Labels , Animals , Cell Line , Endopeptidases , GTP-Binding Proteins/metabolism , Humans , Kidney , Molecular Weight , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Rats , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , TransfectionABSTRACT
Poorly controlled supraventricular arrhythmias in a hypokalaemic 74 year old woman were treated with oral amiodarone. This caused torsades de pointes, and was preceded by marked prolongation of the QT interval. The induction of torsades de pointes by amiodarone is thought to be an idiosyncratic reaction to amiodarone itself which is facilitated by electrolytic abnormalities. The present case, however, indicates the possibility of a pro-arrhythmic effect secondary to an interaction between amiodarone and digoxin.
