Pharmacological Analysis of Mast Cell Mediator and Neurotransmitter Receptors Coupled to Adenylate Cyclase and Phospholipase C on Immunocytochemically-Defined Human Conjunctival Epithelial Cells

ABSTRACT

We sought to establish and immunocytochemically characterize primary cultures of human conjunctival epithelial (HCE) cells, and to determine the types of receptors coupled to adenylate cyclase (AC) and phospholipase C (PLC) present on them which may be stimulated following allergic or inflammatory provocation of the tissue. HCE cells possessed the key epithelial cell surface cytokeratins AE1, AE3 and AE5. Signal transduction studies (n ≥ 3), using agonists and antagonists, revealed the presence of β₂-adrenergic (isoproterenol EC₅₀ = 5.2 nM), prostaglandin E₂ (EC₅₀ = 168 nM) and vasoactive intestinal peptide (EC₅₀ = 0.69 nM) receptors positively coupled to AC in HCE cells. Bradykinin (EC₅₀ 0.83 nM), platelet activating factor (EC₅₀ = 4.5 nM), leukotriene C₄ (EC₅₀ = 300 nM) and histamine_, (EC₅₀ = 3.1 μM) receptors were coupled to PLC (n = 3 for each). These data suggest that HCE cells in vivo may represent target cells for mast cell mediators and certain neurotransmitters which are released into the tear-film upon allergic provocation of the conjunctiva.