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• W2304342227 endingPage "801" @default.
• W2304342227 startingPage "793" @default.
• W2304342227 abstract "Dopamine is a known inhibitor of pituitary melanotropic cells. It reduces Ca(2+) influx by hyperpolarizing the cell membrane and by modulating high- and low-voltage-activated (HVA and LVA) Ca(2+) channels. As a result, dopamine reduces the hormonal output of the cell. However, it is unknown how dopamine affects each of the four different HVA Ca(2+) channel types individually. Moreover, it is unknown whether dopamine interacts with exocytosis independent of Ca(2+) channels. Here we show that dopamine differentially modulates the HVA Ca(2+) channels and that it affects the stimulus-secretion coupling through a direct effect on the exocytotic machinery. Sustained L- and P-type Ba(2+) currents are reduced in amplitude and inactivating N- and Q-type currents acquire different activation and inactivation kinetics in the presence of dopamine. The Q-type current shows slow activation, which is a hallmark for direct G-protein modulation. We used membrane capacitance measurements to monitor exocytosis. Surprisingly, we find that the amount of exocytosis per step depolarization is not diminished by dopamine despite the reduction in Ca(2+) current. To test whether dopamine affects the release machinery downstream of Ca(2+) entry, we stimulated exocytosis by dialyzing cells with buffered high-Ca(2+) solutions. Dopamine increased the amount and the rate of exocytosis. In the first 90 s, the rate of secretion was increased two- to threefold, but it was normalized again at 180 s, suggesting that predominantly vesicles that fuse early in the exocytotic phase are modulated by dopamine. Thus while Ca(2+) channels are inhibited by dopamine, the exocytotic machinery downstream of Ca(2+) influx is sensitized. As a result, release is more effectively stimulated by Ca(2+) influx during dopamine inhibition." @default.
• W2304342227 created "2016-06-24" @default.
• W2304342227 creator A5005318622 @default.
• W2304342227 creator A5012342953 @default.
• W2304342227 creator A5036150377 @default.
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• W2304342227 date "2002-02-01" @default.
• W2304342227 modified "2023-09-24" @default.
• W2304342227 title "Dopamine Modulates Exocytosis Independent of Ca²⁺Entry in Melanotropic Cells" @default.
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• W2304342227 doi "https://doi.org/10.1152/jn.00468.2001" @default.
• W2304342227 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11826047" @default.
• W2304342227 hasPublicationYear "2002" @default.
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