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 chlorpheniramine (an H₁ receptor subtype selective antagonist) but not by 10^-4 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.