Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.
The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.
Neuhaus
Jochen
J
Clinic for Urology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany. neuj@medizin.uni-leipzig.de
Weimann
Annett
A
Stolzenburg
Jens-Uwe
JU
Dawood
Waled
W
Schwalenberg
Thilo
T
Dorschner
Wolfgang
W
D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D016257:Fura-2 / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011968:Receptors, Histamine / Q000145:classification / Q000378:metabolism*; D001743:Urinary Bladder / Q000166:cytology*
D017442:Histamine Agonists; D011968:Receptors, Histamine; D006632:Histamine; D002217:Carbachol; D002118:Calcium; D016257:Fura-2