Cell-specific expression of the IP(3) receptor gene family in the kidney.
OBJECTIVE
The localization of inositol trisphosphate (IP(3)) receptor isoforms, types 1-3, in the kidney and their role in the regulation of the intracellular calcium concentration - [Ca(2+)](i) - are discussed.


METHODS
Immunohistological studies with isoform-specific antibodies were performed to reveal the localization of IP(3) receptor isoforms. To examine the role of IP(3) receptor type 1 in the glomeruli, the responses of [Ca(2+)](i) to hormonal stimuli were examined in IP(3) receptor type 1 knockout mice.


RESULTS
In the immunohistological study, type 1 receptor was present in arteries, afferent arterioles, and mesangial cells. Double staining with antibodies against aquaporin 2 and IP(3) type 2 receptor revealed that type 2 receptor was localized mainly in the intercalated cells. The type 3 receptor showed characteristic intracellular localization in the collecting duct cells of the cortex to the outer medulla. Immunostaining of type 3 receptor was most intense in the cytoplasm on the basolateral membrane side and was not seen on the apical side. The responses of [Ca(2+)](i) to angiotensin II and endothelin in the glomeruli were markedly attenuated in IP(3) receptor type 1 knockout mice.


CONCLUSIONS
The three isoforms of the IP(3) receptor showed distinctive localization in the kidney, and the type 1 receptor plays a major role in the regulation of [Ca(2+)](i) in the glomeruli. The physiological significance of the cell-specific localization, however, remains to be determined.
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
M
M
Hayashi
T
T
Monkawa
T
T
Saruta
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015220:Calcium Channels; C506926:ITPR1 protein, human; C506927:ITPR2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium