The positive control of cell proliferation by the interplay on calcium ions and cyclic nucleotides. A review.
Calcium, cyclic AMP, and cyclic GMP do not seem to be involved in proliferative activation of postmitotic differentiated cells. Instead, they are intracycle regulators, and we propose the following working model of their control of the initiation of DNA synthesis. While a role for cyclic GMP cannot yet be defined, a brief postmitotic burst of its synthesis might serve to prevent certain activated cells (e.g. 3T3 mouse cells) from being diverted into a nonproliferating (but still activated) G0 state (Figs. 1 and 17). In a latter part of the G1 phase, something happens to stimulate briefly the synthesis of cyclic AMP which, in turn, drives calcium ions from the mitochondria into the  cytosol to activate newly synthesized thymidylate synthetase (or other primed enzymic assemblies) (Fig. 1). Having "turned on" their target enzymes, the accumulated cyclic AMP is destroyed and the excess calcium ions are reaccumulated by the mitochondria to avoid interfering with succeeding reactions. This model predicts that persistent changes in cyclic AMP metabolism and the respiration-linked, calcium-accumulating (ion-buffering) activity of mitochondria may be responsible for the sustained growth of tumors.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D003857:Deoxyuridine / Q000494:pharmacology; D005467:Floxuridine / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D013938:Thymidine Monophosphate / Q000494:pharmacology
D010281:Parathyroid Hormone; D011453:Prostaglandins; D005467:Floxuridine; D003208:Concanavalin A; D013938:Thymidine Monophosphate; D003994:Bucladesine; D013006:Growth Hormone; D004247:DNA; D010869:Pindolol; D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine; D003857:Deoxyuridine