Neurotransmitters and neuropeptides stimulate inositol phosphates and intracellular calcium in cultured human nonpigmented ciliary epithelium.
The effects of several neurotransmitters and neuropeptides on the inositol phosphate/diacylglycerol pathway were examined in human nonpigmented ciliary epithelial cells. Maximal stimulation of inositol phosphate formation by vasopressin (approximately 3-fold), carbachol (approximately 2-fold) and histamine (approximately 5-fold) was observed only after cells had been confluent for at least six days. In contrast, a response to bombesin (approximately 3-fold) declined with extended time in confluent culture. Inositol monophosphate, inositol bisphosphate, and inositol trisphosphate all were stimulated by these agonists. Dose-response studies showed a close correlation between the EC50s of the different agonists when elevation of inositol phosphates was compared to stimulation of intracellular Ca2+, with the exception of bombesin. Preliminary pharmacologic characterization of the receptors for vasopressin, carbachol, and bombesin provided rank order of potencies for selective agonists and antagonists. The data suggest that the muscarinic receptor on human NPE cells is the M3 subtype, whereas the vasopressin receptor, as defined by its linkage to the inositol phosphate/diacylglycerol pathway, is the V1 subtype.
Crook
R B
RB
Department of Ophthalmology, University of California, San Francisco.
Polansky
J R
JR
D000700:Analgesics / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction
D000700:Analgesics; D002614:Chelating Agents; D007211:Indoles; D007295:Inositol Phosphates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; C059587:Indo-1 pentaacetoxymethyl ester; D002118:Calcium