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Query: UNIPROT:P06889 (Mol)
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The effects of angiotensin II (AII) on prolactin release and arachidonate liberation were studied in anterior pituitary cells preincubated with [3H]arachidonate to label the cellular phospholipids. AII increased prolactin release and [3H]arachidonate liberation over similar concentration ranges with the dynamics of these two events proving identical. Dopamine attenuated both prolactin release and [3H]arachidonate liberation. The diacylglycerol lipase inhibitor RHC80267 decreased AII-stimulated prolactin release and arachidonate liberation. Further evidence that AII-induced release of arachidonate is mediated by a diacylglycerol lipase is suggested by the finding that AII increased [14C]stearate liberation from cells prelabeled with the fatty acid. Although arachidonate itself may have some role in prolactin secretion, it is likely that arachidonate metabolites are more directly involved because BW755c and AA861, inhibitors of arachidonate metabolite formation, increased AII-stimulated arachidonate liberation, but decreased prolactin release.
Mol Cell Endocrinol 1988 May
PMID:Angiotensin II increases pituitary cell prolactin release and arachidonate liberation. 313 14

The in vitro effect of synthetic diacylglycerol (DG) and phorbol myristate acetate (PMA), potent stimulators of protein kinase C, was studied on prolactin release. These substances increased, in a concentration-dependent manner, prolactin release from primary cultures of anterior pituitary cells. Similarly, exposure of pituitary cells to phospholipase C, which liberates endogenous DG from various substrates, also enhanced prolactin release. The effect of Ca2+ mobilization on PMA-, synthetic DG- or phospholipase C-induced prolactin release was examined. A23187 at 400 nM or 2 ng/ml maitotoxin, a Ca2+ channel activator, did not affect prolactin release by themselves, but enhanced the release of prolactin induced by DG, PMA or phospholipase C. The stimulatory effects of DG, PMA and phospholipase C on prolactin release were reduced by co-incubation with dopamine. These results suggest that the presumed activation of protein kinase C by DG and mobilization of Ca2+ may be synergistically involved in the regulation of prolactin release. Dopamine appears to inhibit prolactin release at a point distal to the DG-enhanced stimulation of the process.
Mol Cell Endocrinol 1985 May
PMID:Calcium mobilization potentiates prolactin release induced by protein kinase C activators. 315 6

The metabolism and release of dopamine by rat mesostriatal and mesolimbic dopamine neurons were determined after 2 or 14 days of subcutaneous administration via Alzet minipumps of a selective (CGS 15855A) or nonselective (apomorphine) dopamine autoreceptor agonist. Bioassays and high performance liquid chromatography assays showed that each drug was accurately delivered for the 2- and 14-day periods. CGS 15855A levels in the plasma and brain increased with increases in the daily dose given, although plasma levels of CGS 15855A at 14 days were less than those at 2 days for each dose. Striatal dopamine metabolism and release, assessed with dihydroxyphenylacetic acid and 3-methoxytyramine concentrations, respectively, were suppressed by 2-day treatments of 50-200 micrograms/day CGS 15855A or 250 micrograms/day apomorphine. These suppressions were potentiated by acute challenge with 1 mg/kg intraperitoneally of CGS 15855A or 2 mg/kg subcutaneously of apomorphine. In contrast, dopamine metabolism and release were unchanged after 14 days of administration of 40-400 micrograms/day of CGS 15855A or 250 micrograms/day of apomorphine, even when plasma levels of drug were as high as at 2 days. Dopamine release was decreased in only one of six groups 30 min after an additional acute injection of the agonist given for 14 days, whereas dopamine metabolism was decreased in five of six groups. Striatal dopamine levels were increased 20-57% after 14 but not 2 days of cgs 15855A followed by acute challenge with the vehicle or CGS 15855A injections. Thus, the responsiveness of dopamine neurons to the release-suppressing properties of dopamine autoreceptor agonists is mostly attenuated between 2 and 14 days of treatment. The ability of chronic CGS 15855A treatments to increase dopamine levels and, with acute CGS 15855A, to decrease DOPAC levels, indicates that autoreceptor control of dopamine metabolism is partly retained after chronic autoreceptor agonism.
Mol Pharmacol 1988 Jun
PMID:Dopamine release and metabolism after chronic delivery of selective or nonselective dopamine autoreceptor agonists. 338 82

PC12 cells are spherical when cultured on plastic, but flatten and spread extensively when cultured on extracellular matrix (ECM) produced by bovine corneal endothelial cells. We previously demonstrated that cells which have spread on ECM release more dopamine and contain less intracellular dopamine than cells which are rounded on plastic cultureware. Glucocorticoids increase dopamine production in PC12 cells presumably via an increase in tyrosine hydroxylase gene transcription. We questioned whether cell shape as determined by ECM would change the response of PC12 cells to glucocorticoids. Dopamine release and cell content were measured by a radioenzymatic assay in serum-free cultures of PC12 cells on ECM and plastic treated with various glucocorticoids in a dose-response fashion for 24 or 48 h. In addition, the response of cells on both substrata to one dose of dexamethasone was examined from 3-48 h. PC12 cells on ECM and plastic exhibited a dose-related increase in dopamine release and content when treated for 24 h with corticosterone or for 48 h with dexamethasone, corticosterone or cortisol. The ED50s for dexamethasone- and corticosterone-stimulated release and content were similar for cells on ECM and plastic as were the doses at which the first significant increases were detected. The average times at which the first significant increase in release and content occurred were also similar for cells on ECM and plastic. PC12 cells on ECM continue to release more dopamine and store less dopamine than cells on plastic with glucocorticoid treatment. However, glucocorticoid-treated cells on ECM showed a greater percent increase over ECM controls in the cell content of dopamine, whereas glucocorticoid-treated cells on plastic showed a greater percent increase over controls in the release of dopamine. It is hypothesized that glucocorticoids increase dopamine production to a similar extent in cells on ECM and plastic, but that storage is facilitated in cells on ECM.
Mol Cell Endocrinol 1987 Apr
PMID:Glucocorticoid stimulation of dopamine production in PC12 cells on extracellular matrix and plastic. 356 53

[2-3H]Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine) bound to a single class of binding sites in synaptic vesicles isolated from bovine corpus striatum, with an apparent dissociation constant (Kd) of 2.3 nM and a Bmax of 15.1 pmol/mg of protein determined at equilibrium. Kinetic determination of the equilibrium dissociation constant yielded a value of 5.4 nM. ATP had no effect on the apparent Kd or Bmax, nor did it alter the kinetics of association or dissociation. Dopamine, serotonin, and other substrates for transport into synaptic vesicles inhibited binding at concentrations that were several orders of magnitude higher than their Km values for transport in the presence of ATP. The potent uptake blocker reserpine inhibited with a Ki of 340 nM in the absence of ATP, but biphasic inhibition, with Ki values of 3.2 and 345 nM, was observed in the presence of ATP. With incubation times of 24 hr, the potency of reserpine as an inhibitor of binding in the absence of ATP is increased by 1 to 2 orders of magnitude, implying a slow association rate for reserpine in the absence of nucleotide. These results suggest that dihydrotetrabenazine interacts with the catecholamine/serotonin porter in synaptic vesicles, although the binding site is probably not identical to that involved in active transport of substrate.
Mol Pharmacol 1986 Sep
PMID:[3H]Dihydrotetrabenazine binding to bovine striatal synaptic vesicles. 374 8

Histamine-N-methyltransferase, a major histamine-degrading enzyme in the skin, was purified from guinea pig skin about 150-fold. The enzymological characteristics including pH optimum, Km values for substrates, and molecular weight were almost consistent with those reported in the brain. Regulatory mechanism of the enzyme activity by biogenic amines was investigated using the purified specimen. Serotonin, tryptamine, and 5-methoxytryptamine intensely inhibited the activity while tryptophan, melatonin, N-acetylserotonin, tryptophol, and 5-hydroxyindole acetic acid had no significant effects. Dopamine, tyramine, 3-methyltyramine, and phenylethylamine also inhibited the activity while no particular effects were obtained by adrenaline, noradrenaline, tyrosine, and DOPA. Spermidine and cadaverine caused significant but weaker inhibition. These amines acted competitively with respect to histamine, although varying manners were observed with respect to S-adenosyl-L-methionine. From these results, it was concluded that the enzyme activity was inhibited by such compounds in which a certain chemical structure, CH2-CH2-NH2 group neighboring the hydrophobic group, was contained. A possible mechanism of inhibition by the amines is postulated, and possible roles of such compounds in the inflammation by impairing the histamine metabolism is discussed.
Exp Mol Pathol 1986 Dec
PMID:Regulation of the activity of histamine-N-methyltransferase from guinea pig skin by biogenic amines. 379 10

In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind [3H]spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol. The degree of D2 dopamine receptor photoinduced inactivation by azidoclebopride was not significantly affected by scavengers such as p-aminobenzoic acid and dithiothreitol. Furthermore, irradiation of striatal membranes with a concentration of azidoclebopride sufficient to inactivate dopamine D2 receptors by 60% did not significantly reduce dopamine D1, serotonin (S2), benzodiazepine, alpha 1- or beta-noradrenergic receptors. This study describes the use of a novel and selective photoaffinity ligand for brain dopamine D2 receptors. The molecule, in radiolabeled form, may aid in the molecular characterization of these receptors.
Mol Pharmacol 1985 Feb
PMID:A photoaffinity ligand for dopamine D2 receptors: azidoclebopride. 396 68

Physiological, pharmacological, histochemical and biochemical studies indicate that dopamine receptors are heterogenous in the central nervous system with each individual functions. This review describes pharmacological and biochemical characteristics of dopamine receptors, particularly in canine caudate nucleus, which have been studied in our laboratory with a brief comparison to the current studies by other workers in similar research fields. Two distinct dopamine receptors have been characterized by means of [3H]dopamine binding to the synaptic membranes from canine caudate nucleus. One of the receptors with a Kd of about 3 muM for dopamine may be associated with adenylate cyclase and referred to as D2 receptor. The other receptor with a Kd of about 10 nM for dopamine is independent of adenylate cyclase and referred to as D2. A photochemical irreversible association of [3H]dopamine with the membraneous receptors makes it possible to separate D1 and D2 receptors from one another by gel filtration on a Sephadex G-200 column after solubilization with Lubrol PX. On the basis of selective inhibition of [3H]dopamine binding to D1 and D2 receptors, dopamine antagonists can be classified into three classes: D1-selective (YM-09151-2), D2-selective (sulpiride) and nonselective (haloperidol, chlorpromazine). Effects of these typical antagonists on the metabolism of rat brain dopamine suggest that D1 receptor is more closely associated with the neuroleptic-induced increase in dopamine turnover. Studies with 28 benzamide derivatives and some classical neuroleptics reveal that apomorphine-induced stereotypy displays a greater association with D1 than with D2 receptors. Dopamine-sensitive adenylate cyclase in canine caudate nucleus can be solubilized with Lubrol PX in a sensitive form to either dopamine. Gpp(NH)p or fluoride Sephadex G-200 gel filtration separates adenylate cyclase from D1 receptors with a concomitant loss of dopamine sensitivity. Addition of the D1 receptor fraction to the adenylate cyclase restores the responsiveness to dopamine. The solubilized dopamine-unresponsive adenylate cyclase can be further separated into two distinct fractions by a batch-wise treatment with GTP-sepharose: a catalytic unit which does not respond to fluoride, and a guanine nucleotide regulatory protein. The regulatory protein confers distinct responsiveness to Gpp(NH)p and fluoride upon adenylate cyclase. These results indicate that dopamine-sensitive adenylate cyclase is composed of at least three distinct units; D1 receptor, guanine nucleotide regulatory protein and adenylate cyclase.
Mol Cell Biochem 1982 Mar 19
PMID:Dopamine receptors in canine caudate nucleus. 612 40

1. Dopamine has been reported to exist in unusually large quantities in Aplysia gill. The physiological role of this neurotransmitter in this organ was examined. 2. The addition of dopamine to a gill perfusate results in the contractions of the lateral and medial external pinnule muscles, the circular and longitudinal muscles of the afferent vessel, and the circular muscles of the efferent vessel. 3. Dopamine-induced contractions persist after chemical synaptic transmission is eliminated in the gill. This suggests that excitatory dopamine receptors are present on gill smooth muscle fibers themselves. 4. Dopamine also potentiates the gill response to action potentials in single identified gill motoneurons. Evidence presented suggests that muscle contractions and modulation of motoneuron contractions are independent phenomena. 5. While modulation may in part be mediated by increases in excitatory junction potential (EJP) amplitude, in many cases large increases in muscle contractions occur while the enhancement of EJPs is disproportionately small. 6. Dopamine's ability to produce muscle contractions suggests that there may be dopaminergic motoneuron innervation of the gill. We suggest that dopamine's modulatory actions may be mediated via modification of excitation-contraction coupling in smooth muscle fibers.
Cell Mol Neurobiol 1982 Dec
PMID:Dopamine produces muscle contractions and modulates motoneuron-induced contractions in Aplysia gill. 613 84

Prolactin secretion from ovine pituitary cell cultures was stimulated by thyrotropin-releasing hormone (TRH) (10(-10)-10(-7) M) with a half-maximal effect at approximately 2.5 X 10(-9) M. A maximally effective concentration of TRH produced a peak secretory response, 5-10-fold stimulation over basal release, within 15 min. Dopamine (10(-10)-10(-7) M) but not somatostatin caused a dose-related inhibition of TRH (10(-8) M) stimulated prolactin release. Both dopamine (10(-7) M) and somatostatin (10(-7) M) inhibited basal secretion from the cells. TRH did not significantly increase pituitary cell cyclic AMP levels under any of the conditions tested. Stimulation of prolactin secretion by TRH was not prevented when Ca2+ was omitted from the incubation medium. Dopamine inhibited secretion induced by TRH under low Ca2+ conditions. Our results are consistent with a hypothesis that TRH may stimulate prolactin secretion via release of intracellular Ca2+ rather than increased cellular Ca2+ uptake, and imply that dopamine inhibition involves a lowering of intracellular Ca2+ levels.
Mol Cell Endocrinol 1984 Jun
PMID:Studies of TRH-induced prolactin secretion and its inhibition by dopamine, using ovine pituitary cells. 614 44


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