Expression and function of alpha1-adrenoceptor subtypes in the porcine renal artery.
We investigated the expression and function of alpha1-adrenoceptor subtypes in the porcine renal artery. Reverse transcription polymerase chain reaction (RT-PCR) and nucleotide sequencing indicated that the mRNAs for alpha1a- and alpha1b-adrenoceptors were expressed in the porcine renal artery. Chloroethylclonidine, an alpha1B- and alpha1D-adrenoceptor antagonist, partially inhibited the phenylephrine-induced contraction, while 3 nM BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]dec ane-7,9-dione dihydrochloride), an alpha1D-adrenoceptor antagonist, had no effect. In contrast, 5-methylurapidil, an alpha1A-adrenoceptor antagonist, induced a rightward shift of the phenylephrine concentration-response curve. The simultaneous measurement of cytosolic Ca2+ concentration ([Ca2+]i) and tension revealed that chloroethylclonidine pretreatment abolished the phenylephrine-induced increases in [Ca2+]i and tension in the Ca2+-free solution. The application of 5-methylurapidil (3 nM) to the chloroethylclonidine-pretreated strips completely inhibited the 3 microM phenylephrine-induced [Ca2+]i and tension increase in normal PSS. We concluded that both alpha1A- and alpha1B-adrenoceptors mediate the phenylephrine-induced contraction of the porcine renal artery accompanied by an increase in [Ca2+]i, and that alpha1A-adrenoceptors cause Ca2+ influx whereas alpha1B-adrenoceptors mainly mediate Ca2+ release.
Zhou
Y
Y
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nishimura
J
J
Seguchi
H
H
Hirano
K
K
Kanaide
H
H
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics* / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium