Distribution of alpha1-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular contraction in human renal artery.
This study was intended to quantify the amounts of the alpha1-adrenoceptor subtype mRNAs in human renal artery and to demonstrate the distribution of receptor subtypes responsible for the contraction of the renal artery. RNase protection assay showed that the mean amount of alpha1a mRNA was much greater than that of alpha1b or alpha1d mRNAs in both the main and branch renal arteries. However, the abundance of alpha1a mRNA in human renal artery was much less than in our previous data in the prostate. In situ hybridization showed that all alpha1 subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the branch artery. However, the intensity of signals for alpha1d and alpha1b antisense RNAs probes was lower than that for the alpha1a antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an alpha1A/L-adrenoceptor selective antagonist, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction, and prazosin showed relatively low affinity with a pA2 value of 8.8. These data suggest that the alpha1A/L-adrenoceptor mediates primarily those responses to noradrenaline in this artery. The other alpha1-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.
Moriyama
N
N
Department of Urology, Faculty of Medicine, The University of Tokyo, Japan.
Kurooka
Y
Y
Nasu
K
K
Akiyama
K
K
Takeuchi
T
T
Nishimatsu
H
H
Murata
S
S
Murayama
T
T
Tsujimoto
G
G
Kawabe
K
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D015347:RNA Probes; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics* / Q000502:physiology; D012077:Renal Artery / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D015347:RNA Probes; D018340:Receptors, Adrenergic, alpha-1; D012313:RNA; D009638:Norepinephrine