Stimulation of D2 dopamine receptors decreases intracellular calcium levels in rat anterior pituitary cells but not striatal synaptosomes: a flow cytometric study using indo-1.
An important question is whether all D2 dopamine (DA) receptors employ the same signal transduction mechanisms. Anterior pituitary cells and striatal synaptosomes, which possess pharmacologically similar D2 DA receptors, were compared with respect to the effect of D2 DA receptor stimulation on free intracellular Ca2+ levels [( Ca2+]i). Flow cytometry, in combination with either the fluorescent calcium indicator indo-1 or fluorescent voltage-sensitive dyes, was used to measure [Ca2+]i and to detect changes in membrane potential. In subpopulations of anterior pituitary cells, increases in [Ca2+]i were produced by elevated K+, veratridine, thyrotropin-releasing hormone, and BAY K 8644. These increases were blocked by nifedipine, suggesting the involvement of L-type voltage-sensitive calcium channels (VSCC's). In 10-15% of the cells, D2 agonists decreased resting [Ca2+]i, reversed stimulus-induced increases in [Ca2+]i, and caused a hyperpolarization. In striatal synaptosomes, elevated K+ and veratridine also increased [Ca2+]i. However, the K+-induced increase was eliminated if choline was substituted for Na+ in the medium, suggesting that Ca2+ entry in response to sustained K+ depolarization resulted from reversal of Na+/Ca2+ exchange. Nifedipine and verapamil inhibited K+-induced increases in [Ca2+]i only at concentrations greater than 10 microM, while omega-conotoxin had no effect. D2 agonists had no effect on resting or stimulated [Ca2+]i but did hyperpolarize 10-20% of the synaptosomes, indicating that D2 DA receptors are functional in this preparation. The ability of pituitary but not striatal D2 DA receptors to modulate [Ca2+]i may reflect the fact that the two systems differ with respect to pathways for Ca2+ influx.
Wolf
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Center for Cell Biology, Sinai Research Institute, Detroit, Michigan 48235.
Kapatos
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium; D002118:Calcium