['which', 'membrane', 'phosphatidylethanolamine', '(PE)', 'is', 'stepwise', 'methylated', 'to', 'phos-', 'phatidylcholine', '(PC)', '(41);', 'and', '(b)', 'a', 'phosphatidylinositol', '(PI)-phosphatidic', 'acid', '(PA)', 'system', 'in', 'which', 'hydrolysis', 'of', 'PI’', 'forming', 'inositol', 'and', 'PA', 'results', 'in', 'gland', 'secretions', '(42).', 'Both', 'of', 'these', 'systems', 'have', 'been', 'linked', 'to', 'Catt', 'gates', 'in', 'the', 'membrane.', 'Catt', 'is', 'critical', 'for', 'release', 'of', 'ACh', 'and', 'amino', 'acid', 'transport', 'in', 'placenta.', 'Therefore,', 'the', 'above', 'systems', 'may', 'play', 'a', 'significant', 'role', 'in', 'placenta.', 'Phospholipid', 'methylation', 'and', 'human', 'syncytiotrophoblast', '(figures', '4', 'and', '5)', 'Phospholipids', 'are', 'major', 'components', 'of', 'biomembranes', 'and', 'provide', 'the', 'fluid', 'matrix', 'for', 'protein', 'movement', 'and', 'organization.', 'Membrane', 'fluidity', 'is', 'closely', 'related', 'to', 'biological', 'and', 'biochemical', 'processes', 'such', 'as', 'transport', 'of', 'chemicals', '(43,44).', 'Physiological', 'and', 'biochemical', 'events', 'that', 'regulate', 'membrane', 'fluidity', 'are', 'stil]', 'unknown.', 'One', 'development', 'is', 'the', 'discovery', 'that', 'enzymatic', 'methylation', 'of', 'phosphatidylethanolamine.in.erythrocyte', 'membranes', 'induces', 'a', 'marked', 'increase', 'in', 'membrane', 'fluidity', '(45).', 'Further,', 'binding', 'of', 'g-adrenergic', 'agonists', 'to', 'B-adrenergic', 'receptors', 'in', 'reticulocytes', 'facilitates', 'the', 'lateral', 'mobility', 'and', 'coupling', 'of', 'the', 'receptor', 'with', 'adenylate', 'cyclase', '(45).', 'Two', 'methyltransferases', 'are', 'involved', 'in', 'the', 'conversion', 'of', 'phosphatidyl-', 'ethanolamine', 'to', 'phosphatidylcholine', '(46).', 'These', 'enzymes', 'are', 'asymmetrically', 'distributed', 'in', 'erythrocyte', 'membranes', '(46).', 'The', 'first', 'enzyme', 'converts', 'phospha-', 'tidylethanolamine', 'to', 'phosphatidyl-N-monomethylethanolamine,', 'and', 'it', 'faces', 'the', 'cytoplasmic', 'side,', 'The', 'second', 'enzyme', 'adds', 'two', 'additional', 'groups', 'from', 'S-adenosyl-', 'L-methionine', 'to', 'form', 'phosphatidylcholine,', 'and', 'it', 'is', 'located', 'on', 'the', 'external', 'surface', 'of', 'the', 'erythrocyte', 'membrane', '(47,48).', 'Thus,', 'translocation', 'of', 'phospho-', 'lipids', 'from', 'the', 'inside', 'to', 'the', 'outside', 'of', 'the', 'membrane', 'is', 'facilitated', 'by', 'a', 'stepwise', 'methylation', 'of', 'phospholipids,', 'and', 'this', 'also', 'increases', 'membrane', 'fluidity.', 'Human', 'syncytiotrophoblast', 'is', 'a', 'suitable', 'tissue', 'for', 'studying', 'the', 'role', 'of', 'ACh', 'in', 'the', 'above', 'phenomenon.', 'Very', 'small', 'concentrations', 'of', 'ACh', 'released', 'from', 'placenta', 'may', 'stimulate', 'the', 'cholinergic', 'receptor', 'and', 'accelerate', 'enzymatic', 'methylations', 'of', 'phospholipids,', 'which', 'in', 'turn', 'may', 'unmask', 'transport', 'systems.', 'Choline', 'acetyltransferase', 'inhibitors', 'should', 'decrease', 'these', 'enzymatic', 'methyla-', 'tions', 'in', 'situ.', 'Antimuscarinic', 'agents', 'shoutd', 'block', 'the', 'effects', 'of', 'ACh', 'on', 'enzymatic', 'methylations.', 'Nicotine', 'in', 'smal?', 'concentrations', 'may', 'accelerate', 'these', 'enzymatic', 'methylations,', 'but', 'higher', 'concentrations', 'may', 'decrease', 'them.', 'According', 'to', 'our', 'investigations,', 'two', 'phospholipid', 'N-methyltransferases', 'are', 'present', 'in', 'human', 'placental', 'villus', '(49-51).', 'The', 'two', 'phospholipid', 'methyl', 'transferases', 'found', 'in', 'the', 'plasma', 'membrane', 'of', 'placental', 'microvillus', 'tissue', 'have', 'properties', 'similar', 'to', 'those', 'found', 'in', 'adrenal', 'microsomes', '(46),', 'liver', 'microsomes', '(52,53),', 'and', 'human.', 'Sperniatozoa', '(54,55).', 'Further', 'inhibition', 'of', 'phospholipid', 'methylation', 'decreased', 'the', 'uptake', 'of', 'AIB', 'by', 'the', 'placental', 'villus', '(49-51).', 'These', 'observations', 'indicate', 'that', 'phospholipid', 'methylation', 'is', 'linked', 'to', 'amino', 'acid', 'uptake.', 'The', 'effects', 'of', 'cholinergic', 'agonists', '@', 'and', 'antagonists', 'on', 'phospholipid', 'methylation', 'are', 'in', 'progress.', 'Phosphatidylinositol', '(Pl)-phosphatidic', 'acid', '(PA)', 'system', '(figure', '6)', 'A', 'vast', 'array', 'of', 'hormones', 'and', 'transmitters', 'act', 'at', 'cell', 'surfaces', 'and', 'cause', 'a', 'PI-PA', 'response', 'which', 'is', 'characterized', 'by', 'increased', 'turnover', 'of', 'PI,', 'measured', 'with', 'radioactive', 'inositol', 'or', 'phosphate,', 'and', 'a', 'concurrent', 'increase', 'in', 'PA', 'turn-_', ' ', '  ', '  ', ' ', '50105915']