Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans.
Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H(1) and H(2) receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H(1) and H(2) receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H(1) and H(2) receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H(1) and H(2) receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H(1) and H(2) receptors are variably distributed among different mammalian species and different regions of the heart, whereas H(2) receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H(1) and H(2) receptors. The highly abundant expression of H(2) receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.
Matsuda
Naoyuki
N
Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Jesmin
Subrina
S
Takahashi
Yoshika
Y
Hatta
Eiichiro
E
Kobayashi
Masanobu
M
Matsuyama
Kazuto
K
Kawakami
Nozomi
N
Sakuma
Ichiro
I
Gando
Satoshi
S
Fukui
Hiyoyuki
H
Hattori
Yuichi
Y
Levi
Roberto
R
D000818:Animals; D015870:Gene Expression; D006168:Guinea Pigs; D006321:Heart; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2