Histamine induced contraction of human ciliary muscle cells.
In cultured human ciliary muscle cells we previously showed that histamine, via an H1 receptor, stimulates the production of inositol phosphates and mobilization of intracellular calcium. We further investigated in this study whether histamine would cause contraction of human ciliary muscle cells. Photomicrographs were taken of the ciliary muscle cells before and after exposure to histamine. Cross sectional surface area of the cells was quantified using image analysis software. A decrease in cross sectional surface area was interpreted as an indication of cell contraction. The results of this study indicated that histamine (10(-6) M-10(-4) M) caused contraction of human ciliary muscle cells in a concentration-dependent fashion. The effect of histamine was mediated by the H1 receptor subtype since the histamine effect was antagonized by 10(-6) M chlorphentramine (an H1 receptor subtype selective antagonist) but not by 10(-6) M cimetidine (H2 antagonist) or thioperamide (H3 antagonist). The phospholipase C (PLC) inhibitor, U73122 (10(-6) M) and the intracellular calcium store depleting agent thapsigargin (10(-6) M) both prevented the histamine induced contraction, demonstrating that the activation of PLC and the intracellular calcium release were the key steps necessary for contraction. Our data indicate that in ciliary muscle cells, histamine, via an H1 receptor, activates PLC and increases intracellular calcium, which subsequently causes contraction of the cells.
Markwardt
K L
KL
Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, USA.
Magnino
P E
PE
Pang
I H
IH
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004963:Estrenes / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D004963:Estrenes; D006633:Histamine Antagonists; D011760:Pyrrolidinones; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; D006632:Histamine; D010738:Type C Phospholipases; D002118:Calcium