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McMahon D. 
“Chemical Messengers in Development: A Hypothesis. Differentiation of embryonic cells may be determined by their content of inorganic ions and cyclic nucleotides”. 
Science. 1974;185(4156):1012-21.
An hypothesis concerning differentiation of embryonic cells is presented. It is suggested that the developmental path of a cell is determined by temporal sequences of changes in the concentrations of cyclic nucleotides (cAMP, cGMP) and inorganic ions. The cyclic nucleotides and intracellular inorganic ions combine to regulate metabolism and expression of genes in the developing cell, and they may possibly also regulate each other's concentration within the cell. Initially, inducers bind to receptors on the plasma membrane. Inducers are the molecules that regulate cyclic nucleotide and ion concentrations in the adult and include neuro-transmitters (adrenaline, acetylcholine, serotonin) polypeptide, hormones (insulin, secretin, oxytocin, ACTH etc.), collagen, lectin-like proteins and prostaglandins. Inductions mediated by cell contact are produced by similar molecules attached to the surface of other developing cells. Studies on the sea-urchin embryo are detailed. In one series of experiments the effects of pharmacological agents e.g. dichloro-isoproterenol, dibydroergotanline, propranolol, Koe 592, nylidrine,-isoproterenol, dopamine, ephedrine, phentolamine, tolazoline, phenylephrine, chlorpromazine, fluphenazine, LSD, atropine, hexomethonium, tubocuresine, tetrame thylammonium, on development and cyclic nucleotide metabolism were studied. The results suggested that neurotransmitters may be regulating cyclic nucleotide synthesis. The involvement of cyclic nucleotides in insulin and 3 - acetylpyridine teratogenesis in chick embryo has been studied. The neurotransmitters are suggested to have a more general role in information transmission in eukaryocytes than previously supposed. It is postulated that they have progressed during evolution from being intracellular messengers to a role as inter-cellular messengers for the communication of developmental in formation, and finally for the rapid communication mediated by nerves.
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