Heterotrimeric G proteins involved in the modulation of voltage-dependent calcium channels of neuroendocrine cells.
Various mechanisms have been identified by which hormones and neurotransmitters, interacting with heptahelical receptors, modulate the intracellular Ca2+ concentration in neuronal, endocrine, and neuroendocrine cells. All of them involve heterotrimeric G proteins. Best documented are hormonal stimulations and inhibitions of voltage-dependent Ca2+ channels. Stimulation is caused by agonists interacting with receptors known to induce phosphatidylinositol 4,5-bisphosphate hydrolysis, that is, a PI response. Although the PI response triggers a transient secretion by fast Ca2+ release, the stimulation of Ca2+ channels is assumed to be responsible for prolonged cell responses and for refilling of IP3-sensitive Ca2+ pools after repeated stimulations. Using antisense oligonucleotide microinjection in rat pituitary GH3 cells, Gi2 has been identified as the pertussis toxin-sensitive G protein stimulating Ca2+ channels, whereas Gq/G11 are involved in the concurrent PI response with subsequent protein kinase C activation, which is required for Ca2+ channel stimulation. Inhibitory modulations of Ca2+ channels are assumed to be the basis of inhibitions of transmitter or hormone secretion. Experiments in GH3 cells have revealed that Go subforms composed of alpha o1 x beta 3 x gamma 4 and alpha o2 x beta 1 x gamma 3 are the active G-protein heterotrimers transferring inhibitory signals from muscarinic M4 and somatostatin receptors to the Ca2+ channel, respectively.
Institut für Pharmakologie, Freie Universität Berlin, Germany.
J
J
Hescheler
G
G
Schultz
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006728:Hormones / Q000502:physiology; D007700:Kinetics; D046911:Macromolecular Substances; D009474:Neurons / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology
D015220:Calcium Channels; D006150:Guanine Nucleotides; D006728:Hormones; D046911:Macromolecular Substances; D018377:Neurotransmitter Agents; D016376:Oligonucleotides, Antisense; D019204:GTP-Binding Proteins