bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the L‐menthol binding site in guinea‐pig lung membranes
Authors: Wright C E. , Bowen W P. , Grattan T J. , Morice A H. 
Published: January 2005

L‐Menthol inhibits both neurokinin A and capsaicin‐induced bronchoconstriction in the guinea‐pig and relaxes pre‐constricted guinea‐pig isolated bronchi. Structure‐activity relationships have been defined for the action of (−)‐menthol and related compounds on cold receptors, suggesting an action of L‐menthol at a pharmacological receptor. We have performed radioligand binding studies to characterize the binding sites for [3H]‐L‐menthol in whole cell membranes prepared from guinea‐pig lung tissue.
In kinetic studies, [3H]‐L‐menthol was found to bind rapidly and reversibly. Binding of [3H]‐L‐menthol to lung membranes was found to be time‐dependant becoming fully associated to its site within 40 min, and half‐maximum association occurred within 8 min (t1/2=8 min). [3H]‐L‐menthol was fully dissociated from its binding site within 8 min, (t1/2=2 min).
Inhibition studies presented a pharmacological profile of the ‘L‐menthol site’. Capsaicin, capsazepine, D‐menthol, eugenol, SCH23390 and camphor were all found to displace [3H]‐L‐menthol binding. In contrast WS3, noradrenaline, 5‐hydroxytryptamine, spiperone, flunarazine, bepridil and nicardipine were without effect.
We have identified a L‐menthol binding site in the guinea‐pig, which may represent a site common to a variety of compounds.

British Journal of Pharmacology (1998) 123, 481–486; doi:10.1038/sj.bjp.0701642
Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype
Authors: D'hahan Nathalie , Taouil Karima , Janmot Chantal , Morel Jean‐Emile 
Published: January 2005

In this study we investigated whether long‐term trimetazidine (anti‐ischaemic drug) therapy alters the ventricular myosin heavy chain (MHC) isoform composition in a model of cardiomyopathy.
MHC isoforms were analysed in the native state by electrophoresis in a pyrophosphate buffer. Myosin isoform patterns were studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14 : 6 strain during the time course of the disease and compared with those of healthy golden hamsters (F1B). The correlation between myosin profile and Ca2+‐activated ATPase activity was determined from 220 days.
At the stage of insufficiency (350 days), CMH presented the most abnormal phenotype with 53% V1‐24% V3 compared to 79% V1‐7% V3 (P<0.001), in F1B. Trimetazidine was administered to cardiomyopathic hamsters from the early stage of active disease (30 days) to the congestive stages (220–350 days). Within 65 days, trimetazidine treatment, in CMH and F1B, reduced V1 to a low level (53% and 62%, respectively), which remained constant throughout the treatment. This level was similar to that in 220 and 350 days‐old untreated‐CMH. In sharp contrast, a standard calcium blocker, verapamil, administered to CMH in the same conditions resulted in a higher V1 (about 70%) and higher global myosin ATPase activity from 220 days.
Previous results in terms of hypertrophy and survival, compared to these results, suggest that verapamil and trimetazidine treatments reveal a disssociation between ventricular hypertrophy and isomyosin distribution. In addition, the shift in favour of V3 may not necessarily be an aggravating factor of the disease but an adaptative compensatory event.

British Journal of Pharmacology (1998) 123, 611–616; doi:10.1038/sj.bjp.0701643
Characterization of [3H]‐(2S,2′R,3′R)‐2‐(2′,3′‐dicarboxy‐ cyclopropyl)glycine ([3H]‐DCG IV) binding to metabotropic mGlu2 receptor‐transfected cell membranes
Authors: Cartmell Jayne , Adam Geo , Chaboz Sylvie , Henningsen Robert , Kemp John A. , Klingelschmidt Agnes , Metzler Veit , Monsma Frederick , Schaffhauser Hervé , Wichmann Jürgen , Mutel Vincent 
Published: January 2005

The binding of the new selective group II metabotropic glutamate receptor radioligand, [3H]‐(2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine ([3H]‐DCG IV), was characterized in rat mGlu2 receptor‐transfected CHO cell membranes.
[3H]‐DCG IV binding was pH‐dependent, but was not sensitive to temperature. Saturation analysis showed the presence of a single binding site, with a Kd value of 160 nM and a Bmax value of 10 pmol mg−1 protein. Binding was not sensitive to Na+‐dependent glutamate uptake blockers or Cl−‐dependent glutamate binding inhibitors. Furthermore, up to concentrations of 1 mM, the glutamate ionotropic receptor agonists, N‐methyl‐D‐aspartic acid (NMDA), (S)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) and kainate, did not affect [3H]‐DCG IV binding.
Of the compounds observed to inhibit [3H]‐DCG IV binding, the most potent were the recently described selective group II agonist, (+)‐2‐aminobicyclo‐[3.1.0]hexane‐2,6‐dicarboxylate (LY 354740; Ki value 16 nM) and antagonist, 2‐amino‐2‐(2‐carboxycyclopropan‐1‐yl)‐3‐(dibenzopyran‐4‐yl) propanoic acid (LY 341495; Ki value 19 nM). As expected, for a G‐protein‐coupled receptor, guanosine‐5′‐O‐(3‐thiotriphosphate) (GTPγS) inhibited [3H]‐DCG IV binding in a concentration‐dependent manner, with an IC50 value of 12 nM.
A highly significant correlation was observed between the potencies of compounds able to inhibit [3H]‐DCG IV binding and potencies obtained for agonist activity in a GTPγ35S binding functional assay. In addition, these studies identified a number of compounds with previously unknown activity at mGlu2 receptors, including L(+)‐2‐amino‐3‐phosphonopropionic acid (L‐AP3), L(+)‐2‐amino‐5‐phosphonopentanoic acid (L‐AP5), 3‐((RS)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (R‐CPP), N‐acetyl‐L‐aspartyl‐L‐glutamic acid (NAAG) and (RS)‐α‐methylserine‐O‐phosphate (MSOP).

British Journal of Pharmacology (1998) 123, 497–504; doi:10.1038/sj.bjp.0701647
Effects of rolipram on cyclic AMP levels in alveolar macrophages and lipopolysaccharide‐induced inflammation in mouse lung
Authors: Lucia Gonçalves de Moraes Vera , Singer Monique , Boris Vargaftig B. , Chignard Michel 
Published: January 2005

Our previous work demonstrated that bacterial lipopolysaccharide (LPS), administered by aerosol, induced tumour necrosis factor (TNF‐α) synthesis leading to the infiltration of neutrophils into mice lungs. The treatment of animals with prostaglandin E2 or dibutyryl cyclic AMP impaired both processes. In this study, the target cell for LPS and the modulation by cyclic AMP of TNF‐α production and neutrophil recruitment were investigated.
One hour after inhalation of 2 ml of 0.3 mg ml−1 LPS, TNF‐α levels measured by an ELISA method increased in the bronchoalveolar lavage fluid (BALF) of BALB/c mice, reaching a maximal level 3 h after inhalation. The immunocytochemistry assay demonstrated that 1 h after inhalation, 21.2% of alveolar macrophages collected in the BALF were immunopositive for TNF‐α.
When mice were pretreated, i.p., with 20 mg kg−1 rolipram, a selective inhibitor of phosphodiesterase type 4, TNF‐α levels in the BALF were significantly reduced and only 7.3% of alveolar macrophages were immunopositive for TNF‐α.
Alveolar macrophages from rolipram‐treated mice collected 30 min after inhalation of LPS had a significant increase in the intracellular concentrations of cyclic AMP. This was accompanied by a marked reduction of TNF‐α levels in the BALF that were associated with a suppression of TNF‐α mRNA expression.
Systemic treatment with 20 mg kg−1 rolipram almost completely inhibited the LPS‐induced neutrophil recruitment, whereas it did not significantly reduce the recruitment induced by rmTNF‐α.
Our results indicate that alveolar macrophages may be the target cells for both the induction and control of the lung inflammatory response to LPS. They also suggest that systemic treatment with cyclic AMP‐elevating agents may be useful to control local inflammation resulting from inhalation of bacterial endotoxin.

British Journal of Pharmacology (1998) 123, 631–636; doi:10.1038/sj.bjp.0701649
Mechanisms of acute vasodilator response to bacterial lipopolysaccharide in the rat coronary microcirculation
Authors: Cannon Toby R. , Mann Giovanni E. , Baydoun Anwar R. 
Published: January 2005

In this study the mechanisms of the acute vasodilator action of bacterial lipopolysaccharide (LPS) were investigated in the rat Langendorff perfused heart.
Infusion of LPS (5 μg ml−1) caused a rapid and sustained fall in coronary perfusion pressure (PP) of 59±4 mmHg (n=12) and a biphasic increase in NO levels determined in the coronary effluent by chemiluminescent detection. Both the fall in PP and the increase in NO release were completely abolished (n=3) by pretreatment of hearts with the NO synthase inhibitor L‐NAME (50 μM).
LPS‐induced vasodilatation was markedly attenuated to 5±4 mmHg (n=3) by pretreatment of hearts with the B2 kinin receptor antagonist Hoe‐140 (100 nM).
Vasodilator responses to LPS were also blocked by brief pretreatment with mepacrine (0.5 μM, n=3) or nordihydroguaiaretic acid (0.1 μM, n=4) and markedly attenuated by WEB 2086 (3 μM, n=4).
Thirty minutes pretreatment of hearts with dexamethasone (1 nM), but not progesterone (1 μM), significantly modified responses to LPS. The action of dexamethasone was time‐dependent, having no effect when applied either simultaneously with or pre‐perfused for 5 min before the administration of LPS but inhibiting the response to LPS by 91±1% (n=4) when pre‐perfused for 15 min. The inhibition caused by dexamethasone was blocked by 15 min pretreatment with the glucocorticoid receptor antagonist RU‐486 (100 nM) or by 2 min pre‐perfusion of a 1 : 200 dilution of LCPS1, a selective anti‐lipocortin 1 (LC1) neutralizing antibody.
Treatment with the protein synthesis inhibitor, cycloheximide (10 μM, for 15 min) selectively blunted LPS‐induced vasodilatation, reducing the latter to 3±5 mmHg (n=3), while having no effect on vasodilator responses to either bradykinin or sodium nitroprusside.
These results indicate that LPS‐induced vasodilatation in the rat heart is dependent on activation of kinin B2 receptors and synthesis of NO. In addition, phospholipase A2 (PLA2) is activated by LPS resulting in the release of platelet‐activating factor (PAF) and lipoxygenase but not cyclo‐oxygenase products. These effects are dependent on de novo synthesis of an intermediate protein which remains to be identified.

British Journal of Pharmacology (1998) 123, 637–644; doi:10.1038/sj.bjp.0701650
Pharmacological evidence for the presence of a peripheral postjunctional D2‐like dopamine receptor in rabbit splenic artery
Authors: Zanzottera Daniele , Ferlenga Pierpaolo , Marchini Francesco , Semeraro Claudio 
Published: January 2005

This study was designed to investigate the involvement of postjunctional D2‐like receptors in a rabbit vasculature model used to evaluate the D1‐like agonist activity. Dopamine, epinine and (−)‐DP‐5,6‐ADTN, three mixed D1/D2‐like agonists, fenoldopam and SKF 82958, two selective D1‐like agonists and SKF 89124, a selective D2‐like agonist, were administered cumulatively in precontracted and α/β‐blocked rabbit splenic artery rings in order to evaluate their D1‐like‐mediated vasorelaxant activity before and after pretreatment with the selective D2‐like antagonist YM 09151‐2 (1 nM).
Dopamine (pD2=6.35±0.09), epinine (pD2=6.73±0.13), (−)‐DP‐5,6‐ADTN (pD2=7.56±0.09) and SKF 82958 (pD2=8.55±0.10) reversed completely the U46619‐induced contracture whereas SKF 89124 was inactive up to 10 μM and fenoldopam acted like a partial agonist (pD2=8.31±0.09, α=0.62). The selective D2‐like dopamine receptor antagonist YM 09151‐2 (1 nM) significantly (P<0.05) potentiated the vasorelaxant activity of dopamine (pD2=7.01±0.07), epinine (pD2=7.14±0.08), (−)‐DP‐5,6‐ADTN (pD2=8.19±0.09) and SKF 89124 (40% relaxation at 10 μM), whereas it did not alter the effects of fenoldopam (pD2=8.40±0.09, α=0.68) and SKF 82958 (pD2=8.58±0.08).
The D2‐like antagonist YM 09151‐2 induced the same degree of effect with all the substances tested in both endothelium‐denuded and endothelium‐intact preparations.
The selective D2‐like dopamine receptor agonist SKF 89124 did not produce any intrinsic effect on the splenic artery, but was able to produce a rightward shift of the forskolin‐induced relaxation.
The results of these experiments support the existence of a non‐endothelial postjunctional D2‐like dopamine receptor counteracting the D1‐like‐mediated vasodilatation in rabbit splenic artery, probably by the inhibition of adenylate cyclase.

British Journal of Pharmacology (1998) 123, 730–736; doi:10.1038/sj.bjp.0701651
Salmeterol‐induced desensitization, internalization and phosphorylation of the human β2‐adrenoceptor
Authors: January Bridgette , Seibold Anita , Allal Chafika , Whaley Brenda S. , Knoll Brian J. , Moore Robert H. , Dickey Burton F. , Barber Roger , Clark Richard B. 
Published: January 2005

Partial agonists of the β2‐adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the ability to reassert this activity following the temporary blockade of human β2‐adrenoceptors with antagonist.
We have compared the activation and desensitization of human β2‐adrenoceptor stimulation of adenylyl cyclase induced by salmeterol, adrenaline and salbutamol in a human lung epithelial line, BEAS‐2B, expressing β2‐adrenoceptor levels of 40–70 fmol mg−1, and in human embryonic kidney (HEK) 293 cell lines expressing 2–10 pmol mg−1. The efficacy observed for the stimulation of adenylyl cyclase by salmeterol was only ≈percnt;10% of that observed for adrenaline in BEAS‐2B cells expressing low levels of β2‐adrenoceptor, but similar to adrenaline in HEK 293 cells expressing very high levels of receptors. Salmeterol pretreatment of these cells induced a rapid and stable activation of adenylyl cyclase activity which resisted extensive washing and β2‐adrenoceptor antagonist blockade, consistent with binding to a receptor exosite and/or to partitioning into membrane lipid.
The desensitization and internalization of β2‐adrenoceptors induced by the partial agonists salmeterol and salbutamol were considerably reduced relative to the action of adrenaline. Consistent with these observations, the initial rate of phosphorylation of the receptor induced by salmeterol and salbutamol was much reduced in comparison to adrenaline.
Our data suggest that the reduction in the rapid phase of desensitization of β2‐adrenoceptors after treatment with salmeterol or salbutamol is caused by a decrease in the rate of β2‐adrenoceptor kinase (βARK) phosphorylation and internalization. In contrast, the rate of cyclic AMP‐dependent protein kinase (PKA)‐mediated phosphorylation by these partial agonists appears to be similar to adrenaline.

British Journal of Pharmacology (1998) 123, 701–711; doi:10.1038/sj.bjp.0701658
Direct effects of diazoxide on mitochondria in pancreatic B‐cells and on isolated liver mitochondria
Authors: Grimmsmann T , Rustenbeck I 
Published: January 2005

The direct effects of diazoxide on mitochondrial membrane potential, Ca2+ transport, oxygen consumption and ATP generation were investigated in mouse pancreatic B‐cells and rat liver mitochondria.
Diazoxide, at concentrations commonly used to open adenosine 5′‐triphosphate (ATP)‐dependent K+‐channels (KATP channels) in pancreatic B‐cells (100 to 1000 μM), decreased mitochondrial membrane potential in mouse intact perifused B‐cells, as evidenced by an increase of rhodamine 123 fluorescence. This reversible decrease of membrane potential occurred at non‐stimulating (5 mM) and stimulating (20 mM) glucose concentrations.
A decrease of mitochondrial membrane potential in perifused B‐cells was also caused by pinacidil, but no effect could be seen with levcromakalim (500 μM each).
Measurements by a tetraphenylphosphonium‐sensitive electrode of the membrane potential of rat isolated liver mitochondria confirmed that diazoxide decreased mitochondrial membrane potential by a direct action. Pretreatment with glibenclamide (2 μM) did not antagonize the effects of diazoxide.
In Fura 2‐loaded B‐cells perifused with the Ca2+ channel blocker, D 600, a moderate, reversible increase of intracellular Ca2+ concentration could be seen in response to 500 μM diazoxide. This intracellular Ca2+ mobilization may be due to mitochondrial Ca2+ release, since the reduction of membrane potential of isolated liver mitochondria by diazoxide was accompanied by an accelerated release of Ca2+ stored in the mitochondria.
In the presence of 500 μM diazoxide, ATP content of pancreatic islets incubated in 20 mM glucose for 30 min was significantly decreased by 29%. However, insulin secretion from mouse perifused islets induced by 40 mM K+ in the presence of 10 mM glucose was not inhibited by 500 μM diazoxide, suggesting that the energy‐dependent processes of insulin secretion distal to Ca2+ influx were not affected by diazoxide at this concentration.
The effects of diazoxide on oxygen consumption and ATP production of liver mitochondria varied depending on the respiratory substrates (5 mM succinate, 10 mM α‐ketoisocaproic acid, 2 mM tetramethyl phenylenediamine plus 5 mM ascorbic acid), indicating an inhibition of respiratory chain complex II. Pinacidil, but not levcromakalim, inhibited α‐ketoisocaproic acid‐fuelled ATP production.
In conclusion, diazoxide directly affects mitochondrial energy metabolism, which may be of relevance for stimulus‐secretion coupling in pancreatic B‐cells.

British Journal of Pharmacology (1998) 123, 781–788; doi:10.1038/sj.bjp.0701663
Distribution of P2Y receptor subtypes on haematopoietic cells
Authors: Jin Jianguo , Rao Dasari V , Sistare Frank D. , Kunapuli Satya P. 
Published: January 2005

RT–PCR‐southern hybridization analyses with radiolabelled P2Y receptor cDNAs as probes indicated that the peripheral blood leukocytes and the human umbilical vein endothelial cells express P2Y1, P2Y2, P2Y4 and P2Y6 receptors.
Of the haematopoietic cell lines tested, promonocytic U937 cells express P2Y2 and P2Y6, but not P2Y1 or P2Y4; promyelocytic HL‐60 cells express the P2Y1, P2Y2 and P2Y6 receptors but not the P2Y4 receptor; K562 cells express P2Y1 but not P2Y2, P2Y4 or P2Y6; and Dami cells express P2Y1, P2Y2, P2Y4 and P2Y6 receptors.
Of the peripheral blood leukocytes tested, polymorphonuclear cells express P2Y4 and P2Y6 but not P2Y1 or P2Y2 receptors; monocytes express P2Y1, P2Y2, P2Y4 and P2Y6 receptors and lymphocytes express P2Y1, P2Y2, P2Y4 and P2Y6 receptors.
These results suggest a physiological role for different P2Y receptor subtypes in the extracellular nucleotide‐mediated stimulation of monocytes, neutrophils, lymphocytes and endothelial cells.

British Journal of Pharmacology (1998) 123, 789–794; doi:10.1038/sj.bjp.0701665
Potentiation by DL‐α‐aminopimelate of the inhibitory action of a novel mGluR agonist (L‐F2CCG‐I) on monosynaptic excitation in the rat spinal cord
Authors: Saitoh T. , Ishida M. , Shinozaki H. 
Published: January 2005

Neuropharmacological actions of all the possible stereoisomers of 3′,3′‐difluoro‐2‐(carboxycyclopropyl)glycine (3′,3′‐difluoro‐CCG) were compared with those of the corresponding 2‐(carboxycyclopropyl)glycine (CCG) isomers in the isolated spinal cord of newborn rats. (2S,1′S,2′S)‐ and (2S,1′R,2′S)‐2‐(2‐carboxy‐3,3‐difluorocyclopropyl)glycine (L‐F2CCG‐I and L‐F2CCG‐IV) were the most potent in causing depolarization, their threshold concentrations being approximately 1 μM.
The depolarization evoked by L‐F2CCG‐I (30 μM) was depressed by (+)‐α‐methyl‐4‐carboxyphenylglycine (MCPG, 1 mM (n=4)) to 17±3% of the control: this depolarizing action was not decreased by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 100 μM), and only slightly decreased by high concentrations of D‐2‐amino‐5‐phosphonopentanoic acid (D‐AP5, 100 μM), suggesting that L‐F2CCG‐I activates mainly metabotropic glutamate receptors.
L‐F2CCG‐I preferentially depressed the monosynaptic component of the spinal reflex approximately 3 times more effectively than (2S,1′S,2′S)‐2‐(carboxycyclopropyl)glycine (L‐CCG‐I). The depressant action of L‐F2CCG‐I (0.2 μM–0.7 μM) on monosynaptic excitation was antagonized by (2S,1′S,2′S)‐2‐methyl‐2‐(carboxycyclopropyl)glycine (MCCG, 0.3 mM–1 mM) and (S)‐2‐amino‐2‐methyl‐4‐phosphonobutanoic acid (MAP4, 0.3 mM).
DL‐α‐Aminopimelate (10 and 100 μM) selectively potentiated the depression of monosynaptic excitation caused by L‐CCG‐I (0.2 μM) and L‐F2CCG‐I (0.1 μM). The actions of (2S,1′R,2′R,3≈prime;R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV) (50 nM–0.2 μM), L‐2‐amino‐4‐phosphonobutanoic acid (L‐AP4) (0.3–1 μM), (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD) (1–7 μM) and baclofen (0.1–0.7 μM) were unaffected by DL‐α‐aminopimelate. The threshold concentration for the potentiating actions of DL‐α‐aminopimelate was 3 μM.
The depolarization induced by quisqualate (3 μM, 10 s application) was increased to 115±2% and 137±5% of the control values during combined application of quisqualate with either 30 μM or 100 μM DL‐α‐aminopimelate, respectively.
Following the application and subsequent washout of L‐F2CCG‐I, DL‐α‐aminopimelate (3–100 μM) decreased the amplitude of the monosynaptic component of spinal reflexes in a concentration‐dependent manner, indicating a ‘priming’ effect of L‐F2CCG‐I.

British Journal of Pharmacology (1998) 123, 771–779; doi:10.1038/sj.bjp.0701670
Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis
Authors: Okada Motohiro , Wada Kazumaru , Kiryu Kazuhiro , Kawata Yuko , Mizuno Kazuhisa , Kondo Tuyoshi , Tasaki Hiroichi , Kaneko Sunao 
Published: January 2005

To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4‐dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N‐type Ca2+ channel antagonist, ω‐conotoxin GVIA, a P‐type Ca2+ channel antagonist, ω‐agatoxin IVA, and a Q‐type Ca2+ channel antagonist, ω‐conotoxin MVIIC, on the basal and Ca2+‐ and K+‐evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis.
ω‐Conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50=0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50=9.55 nM). Neither ω‐agatoxin IVA nor ω‐conotoxin MVIIC affected the basal striatal release of dopamine and DOPA.
ω‐Conotoxin GVIA strongly inhibited Ca2+‐evoked striatal dopamine release (IC50=0.40 nM), whereas Ca2+‐evoked striatal DOPA release only was weakly modulated (IC50=10.51 nM). Neither ω‐agatoxin IVA nor ω‐conotoxin MVIIC affected the Ca2+‐evoked release of striatal dopamine and DOPA.
Both ω‐agatoxin IVA and ω‐conotoxin MVIIC inhibited the K+‐evoked release of striatal dopamine (IC50 of ω‐agatoxin IVA=2.65 nM; IC50 of ω‐conotoxin MVIIC=12.54 nM) and DOPA (IC50 of ω‐agatoxin IVA=0.15 nM; IC50 of ω‐conotoxin MVIIC=3.05 nM), whereas ω‐conotoxin GVIA had no effect on the K+‐evoked release of striatal dopamine and DOPA.
An increase in the extracellular Ca2+ and K+ concentrations (Ca2+‐ and K+‐evoked stimulation) did not affect tyrosine hydroxylase activity in vivo.
These findings suggest that striatal DOPA release is neurotransmitter‐like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage‐sensitive Ca2+ channels.

British Journal of Pharmacology (1998) 123, 805–814; doi:10.1038/sj.bjp.0701675