bluuebunny/crossref_metadata_2025_split huggingface dataset:
Operational correlates of prostanoid TP receptor expression in human non‐pregnant myometrium are unaffected by excision site or menstrual cycle status of the donor
Authors: Senchyna Michelle , Crankshaw D J 
Published: January 2005

Cumulative concentration‐effect curves for the selective prostanoid TP receptor agonist, U46619, were constructed in strips of human non‐pregnant myometrium grouped according to tissue excision site (top, lateral wall, lower uterine segment, sub‐serosal or sub‐endometrial), tissue orientation (strips cut either parallel or perpendicular to the serosa) and donor menstrual status (proliferative or secretory phase).
U46619 was excitatory in all tissues. There was no significant difference in either pEC50 or maximum response between groups (P<0.05). The range of pEC50 values was 6.8±0.1 (lateral wall, proliferative phase, n=5) to 7.1±0.3 (lateral wall, secretory phase, n=5). The range of maximum response values was 0.9±0.8 N cm−2 (lateral wall, proliferative phase, n=5) to 3.1±1.0 N cm−2 (lateral wall, secretory phase, n=5).
Saturation binding analyses were conducted using the radiolabelled TP receptor agonist, [125I]‐BOP. Binding parameters were estimated for membranes prepared from human non‐pregnant myometrium excised from the lateral wall and grouped according to donor menstrual status.
There were no significant differences in the mean pKd and [R]tot values for [125I]‐BOP binding between the two groups (proliferative phase: pKd=8.3±0.3, [R]tot=412±319 fmol mg protein−1, n=5; secretory phase: pKd=8.5±0.4, [R]tot=369±192 fmol mg protein−1, n=6; P<0.05).
These data indicate that U46619‐mediated responses in human non‐pregnant myometrium are not influenced by tissue excision site, tissue orientation or donor menstrual status and that [125I]‐BOP binding is not influenced by donor menstrual status. This suggests that the TP receptor population is homogeneous throughout the human non‐pregnant myometrium, and not subject to hormonal regulation.

British Journal of Pharmacology (1999) 128, 1524–1528; doi:10.1038/sj.bjp.0702964
Facilitation by 8‐OH‐DPAT of passive avoidance performance in rats after inactivation of 5‐HT1A receptors
Authors: Otano Ana , García‐Osta Ana , Ballaz Santiago , Frechilla Diana , Del Río Joaquín 
Published: January 2005

Pretraining administration of 8‐hydroxy‐2‐di‐n‐propylamino‐tetralin (8‐OH‐DPAT 0.1 mg kg−1), a 5‐HT1A receptor agonist, or buspirone (1 mg kg−1), a 5‐HT1A receptor partial agonist, markedly impaired passive avoidance retention in rats 24 h later. The effect of 8‐OH‐DPAT was prevented by the 5‐HT1A receptor antagonists, NAN‐190 and WAY‐100635, at doses without any intrinsic effect.
N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ 10 mg kg−1), an alkylating agent that inactivates different G‐protein coupled receptors, impaired retention performance when given 48 h pretraining. The disruptive effect of EEDQ was reversed by 8‐OH‐DPAT or buspirone, given 30 min before training.
Non‐specific actions did not account for 8‐OH‐DPAT‐induced reversal of the EEDQ effect since no significant difference in locomotor activity or in pain threshold was found between rats receiving EEDQ or EEDQ+8‐OH‐DPAT.
When NAN‐190 (1 mg kg−1) or WAY‐100635 (0.5 mg kg−1) were given before 8‐OH‐DPAT to EEDQ‐pretreated animals, the reversal by 8‐OH‐DPAT of EEDQ‐induced retention impairment was still more pronounced. However, no EEDQ reversal by 8‐OH‐DPAT was found when 5‐HT1A receptors were protected by WAY‐100635 (10 mg kg−1) 30 min before EEDQ.
In the hippocampus of EEDQ‐treated rats, 5‐HT7 receptors were less inactivated than 5‐HT1A receptors and significant increases were found in 5‐HT1A but not in 5‐HT7 receptor mRNA levels. Ritanserin and methiothepin (10 mg kg−1 each), antagonists with higher affinity at 5‐HT7 than at 5‐HT1A receptors, prevented the retention impairment induced by EEDQ but did not significantly protect against 5‐HT7 receptor inactivation.
The results indicate that the facilitatory effect of 8‐OH‐DPAT is not mediated through 5‐HT1A receptors and suggest that other 8‐OH‐DPAT‐sensitive receptors could be involved in the dual effect of 8‐OH‐DPAT on passive avoidance performance in rats.

British Journal of Pharmacology (1999) 128, 1691–1698; doi:10.1038/sj.bjp.0702974
An anti‐platelet agent, OPC‐29030, inhibits translocation of 12‐lipoxygenase and 12‐hydroxyeicosatetraenoic acid production in human platelets
Authors: Ozeki Yasushi , Nagamura Yoshie , Ito Hideki , Unemi Fumiko , Kimura Yukio , Igawa Takehiro , Kambayashi Jun‐ichi , Takahashi Yoshitaka , Yoshimoto Tanihiro 
Published: January 2005

In human platelets, arachidonic acid is mainly metabolized by the two enzyme systems; cyclo‐oxygenase and 12‐lipoxygenase. Cyclo‐oxygenase produces prostaglandin H2 which is further converted to thromboxane B2. 12‐Lipoxygenase synthesizes 12(S)‐hydroperoxyeicosatetraenoic acid which is reduced to 12(S)‐hydroxyeicosatetraenoic acid (12(S)‐HETE).
An anti‐platelet compound, OPC‐29030, dose‐dependently inhibited 12(S)‐HETE production with an IC50 of 0.06±0.01 μM, but not synthesis of thromboxane B2 in human platelets. Although the compound suppressed 12(S)‐HETE production in human platelets, cytosolic 12‐lipoxygenase activity was not inhibited up to 10 μM. Essentially identical data were obtained with a 12‐lipoxygenase of human erythroleukaemia cells which had megakaryocyte/platelet‐like properties.
OPC‐29030 also suppressed production of 5(S)‐HETE, a 5‐lipoxygenase product, in rat basophilic leukaemia cells without inhibiting enzyme activity. It has been shown that 5‐lipoxygenase binds to membrane 5‐lipoxygenase‐activating protein (FLAP) to produce 5(S)‐HETE, and thus FLAP inhibitor suppresses cellular 5(S)‐HETE production.
A FLAP inhibitor, L‐655,238, suppressed platelet 12(S)‐HETE production, but had no effect on the 12‐lipoxygenase activity.
Western blot analysis showed that platelet 12‐lipoxygenase translocated from cytosol to membranes upon thrombin stimulation, and OPC‐29030 suppressed this process in a dose‐dependent manner.
These results suggest that the 12‐lipoxygenase of human platelets binds to FLAP or a similar protein, and OPC‐29030 suppresses 12(S)‐HETE production by inhibiting a certain step of the 12‐lipoxygenase translocation.

British Journal of Pharmacology (1999) 128, 1699–1704; doi:10.1038/sj.bjp.0702976
Selective nitrergic neurodegeneration in diabetes mellitus–a nitric oxide‐dependent phenomenon
Authors: Cellek Selim , Rodrigo José , Lobos Edgar , Fernández Patricia , Serrano Julia , Moncada Salvador 
Published: January 2005

In vitro and in vivo studies have demonstrated a dysfunctional nitrergic system in diabetes mellitus, thus explaining the origin of diabetic impotence. However, the mechanism of this nitrergic defect is not understood.
In the penises of streptozotocin (STZ)‐induced diabetic rats, here, we show by immunohistochemistry that nitrergic nerves undergo selective degeneration since the noradrenergic nerves which have an anti‐erectile function in the penis remained intact.
Nitrergic relaxation responses in vitro and erectile responses to cavernous nerve stimulation in vivo were attenuated in these animals, whereas noradrenergic responses were enhanced.
Activity and protein amount of neuronal nitric oxide synthase (nNOS) were also reduced in the penile tissue of diabetic rats.
We, thus, hypothesized that NO in the nitrergic nerves may be involved in the nitrergic nerve damage, since only the nerves which contain neuronal NO synthase underwent degeneration.
We administered an inhibitor of NO synthase, NG‐nitro‐L‐arginine methyl ester (L‐NAME), in the drinking water of rats for up to 12 weeks following the establishment of diabetes with STZ.
Here we demonstrate that this compound protected the nitrergic nerves from morphological and functional impairment. Our results show that selective nitrergic degeneration in diabetes is NO‐dependent and suggest that inhibition of NO synthase is neuroprotective in this condition.

British Journal of Pharmacology (1999) 128, 1804–1812; doi:10.1038/sj.bjp.0702981
Nitric oxide synthase expression, enzyme activity and NO production during angiogenesis in the chick chorioallantoic membrane
Authors: Pipili‐Synetos Eva , Kritikou Sosanna , Papadimitriou Evangelia , Athanassiadou Aglaia , Flordellis C , Maragoudakis M E 
Published: January 2005

In order to elucidate further the role of nitric oxide (NO) as an endogenous antiangiogenic mediator, mRNA expression of inducible nitric oxide synthase (iNOS), enzyme activity and production of NO were determined in the chick chorioallantoic membrane (CAM), an in vivo model of angiogenesis. In this model, maximum angiogenesis is reached between days 9–12 of chick embryo development. After that period, vascular density remains constant.
Inducible NO synthase (iNOS) mRNA expression, determined by reverse transcriptase polymerase chain reaction (RT–PCR), increased from the 8th day reaching a maximum (70% increase) at days 10–11.
NO synthase activity, determined as citrulline formation in the presence of calcium, also increased from day 8 reaching a maximum around day 10 (100% increase). Similar results were obtained in the absence of calcium suggesting that the NOS determined was the inducible form.
Nitric oxide production, determined as nitrites, increased from day 8 reaching a maximum around day 10 (64% increase) and remaining stable at day 13.
Finally, the bacterial lipopolysaccharide LPS (which activates transcriptionally iNOS), inhibited dose dependently angiogenesis in the CAM. These results in connection with previous findings from this laboratory, showing that NO inhibits angiogenesis in the CAM, suggest that increases in iNOS expression, enzyme activity and NO production closely parallel the progression of angiogenesis in the CAM, thus providing an endogenous brake to control this process.

British Journal of Pharmacology (2000) 129, 207–213; doi:10.1038/sj.bjp.0702986
Lipophilization of somatostatin analog RC‐160 with long chain fatty acid improves its antiproliferative and antiangiogenic activity in vitro
Authors: Dasgupta P , Mukherjee R 
Published: January 2005

The therapeutic potential of the somatostatin analogue RC‐160 having antiproliferative activity, is limited by its short serum half life. To overcome this limitation, fatty acids namely butanoic acid and myristic acid were conjugated to the N‐terminal residue of RC‐160. The lipophilized derivatives of RC‐160 were synthesized, purified by reverse phase HPLC and characterized by ES‐mass spectroscopy. The antiproliferative activity of lipophilized derivatives of RC‐160 on the growth of MIA‐PaCa2 (human pancreatic carcinoma), DU145 (human prostate carcinoma), ECV304 (human umbilical chord endothelioma), as well as their antiangiogenic activity was evaluated in vitro. The relative stability of myristoyl‐RC‐160 towards degradation by proteases and serum was also determined.
Myristoyl‐RC‐160 exhibited significantly higher antiproliferative efficacy than RC‐160, on the above cell lines (P<0.01). Receptor binding assays, demonstrated that the affinity of RC‐160 towards somatostatin receptors remains unaltered by myristoylation. Unlike RC‐160, the myristoylated derivative was found to have significantly greater resistance to protease and serum degradation (P<0.01). Myristoyl‐RC‐160 exhibited significantly greater antiproliferative activity on ECV304, than RC‐160 (P<0.01). Myristoyl RC‐160 could also inhibit capillary tube formation more efficiently than RC‐160 in a dose dependent manner, suggesting that it possessed enhanced antiangiogenic activity in vitro (P<0.001).
Lipophilization of RC‐160 with long chain fatty acids like myristic acid endows it with improved antiproliferative and antiangiogenic activity, stability and therapeutic index.

British Journal of Pharmacology (2000) 129, 101–109; doi:10.1038/sj.bjp.0702990
Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells
Authors: Tahara Atsuo , Tsukada Junko , Tomura Yuichi , Wada Koh‐ichi , Kusayama Toshiyuki , Ishii Noe , Yatsu Takeyuki , Uchida Wataru , Tanaka Akihiro 
Published: January 2005

[3H]‐oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [3H]‐oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration.
Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high‐affinity binding sites with an apparent equilibrium dissociation constant (Kd) of 0.76 nM and a maximum receptor density (Bmax) of 153 fmol mg−1 protein. The Hill coefficient (nH) did not differ significantly from unity, suggesting binding to homogenous, non‐interacting receptor populations.
Competitive inhibition of [3H]‐oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [3H]‐oxytocin in a concentration‐dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu1,6]‐oxytocin>AVP= atosiban>d(CH2)5Tyr(Me)AVP>[Thr4,Gly7]‐oxytocin>dDAVP, and for nonpeptide antagonists was: L‐371257>YM087>SR 49059>OPC‐21268>SR 121463A>OPC‐31260.
Oxytocin significantly induced concentration‐dependent increase in intracellular Ca2+ concentration ([Ca2+]i) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L‐371257, potently and concentration‐dependently inhibited oxytocin‐induced [Ca2+]i increase and hyperplasia. In contrast, the V1A receptor selective antagonist, SR 49059, and the V2 receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin‐induced [Ca2+]i increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin‐induced [Ca2+]i increase and hyperplasia was similar to that observed in radioligand binding assays.
In conclusion, these data provide evidence that the high‐affinity [3H]‐oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca2+]i increase and cell growth. Thus human USMC may prove to be a valuable tool in further investigation of the physiologic and pathophysiologic roles of oxytocin in the uterus.

British Journal of Pharmacology (2000) 129, 131–139; doi:10.1038/sj.bjp.0702996
Involvement of cyclic AMP–PKA pathway in VIP‐induced, charybdotoxin‐sensitive relaxation of longitudinal muscle of the distal colon of Wistar‐ST rats
Authors: Kishi Masami , Takeuchi Tadayoshi , Katayama Hideo , Yamazaki Yasuko , Nishio Hideaki , Hata Fumiaki , Takewaki Tadashi 
Published: January 2005

The intracellular mechanism of vasoactive intestinal peptide (VIP)‐induced, charybdotoxin (ChTx)‐sensitive relaxation of longitudinal muscle of the distal colon of Wistar‐ST rats was studied.
A single pulse or 100 pulses at 10 Hz of electrical field stimulation (EFS) induced rapid transient relaxation or that with a subsequent contraction of the longitudinal muscle in the presence of atropine and guanethidine, respectively.
Rp‐8 bromo cAMPS, an inhibitor of cyclic AMP dependent protein kinase (PKA), at 30 μM inhibited the relaxations induced by EFS with a single or 100 pulses maximally by about 80 or 60%, respectively. It also inhibited VIP (300 nM)‐induced relaxation by 82%.
VIP (100 nM–1 μM) increased the cyclic AMP content of longitudinal muscle myenteric plexus preparations obtained from the distal colon.
ChTx at 100 nM almost completely inhibited 8 bromo cyclic AMP‐induced relaxation of the distal segments.
EFS with two or three pulses at 10 Hz induced inhibitory junction potentials consisting of two phases, rapid and subsequent slow hyperpolarization in the membrane potential of longitudinal smooth muscle cells. Rp‐cAMPS, another inhibitor of PKA, inhibited the delayed slow hyperpolarization. It also inhibited the exogenously added VIP‐induced hyperpolarization of the cell membrane.
Thus, the present study suggests that activation of PKA via activation of VIP receptors is associated with activation of ChTx‐sensitive K+ channels in relaxation of longitudinal muscle of the distal colon of Wistar‐ST rats.

British Journal of Pharmacology (2000) 129, 140–146; doi:10.1038/sj.bjp.0702998
Effects of superoxide anion generators and thiol modulators on nitrergic transmission and relaxation to exogenous nitric oxide in the sheep urethra
Authors: Garcia‐Pascual A , Labadia A , Costa G , Triguero D 
Published: January 2005

The effects of superoxide anion generators, the nitric oxide (NO) scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoine‐1‐oxyl 3‐oxide (carboxy‐PTIO), the specific guanylate cyclase inhibitor 1H‐[1,2,4]‐oxadiazole‐[4,3‐a]‐quinoxalin‐1‐one (ODQ), and thiol modulating agents were investigated on relaxations induced by nitrergic stimulation and exogenous NO addition in the sheep urethra.
Methylene blue (MB, 10 μM), pyrogallol (0.1 mM) and xanthine (X, 0.1 mM)/xanthine oxidase (XO, 0.1 u ml−1) inhibited NO‐mediated relaxations, without affecting those induced by nitrergic stimulation. This resistance was not diminished following inhibition of endogenous Cu/Zn superoxide dismutase (Cu/Zn SOD) with diethyldithiocarbamic acid (DETCA, 3 mM), which almost abolished tissue SOD activity.
Carboxy‐PTIO (0.1–0.5 mM) inhibited NO‐mediated relaxations but had no effect on responses to nitrergic stimulation, which were not changed by treatment with ascorbate oxidase (2 u ml−1).
Relaxations to NO were reduced, but not abolished, by ODQ (10 μM), while nitrergic responses were completely blocked.
The thiol modulators, ethacrynic acid (0.1 mM), diamide (1.5 mM), or 5,5′‐dithio‐bis (2‐nitrobenzoic acid) (DTNB, 0.5 mM), and subsequent treatment with dithiothreitol (DTT, 2 mM) had no effect on responses to nitrergic stimulation or NO. In contrast, N‐ethylmaleimide (NEM, 0.2 mM) markedly inhibited both relaxations.
L‐cysteine (L‐cys, 0.1 mM) had no effect on responses to NO, while it inhibited those to nitrergic stimulation, in a Cu/Zn SOD‐independent manner.
Our results do not support the view that the urethral nitrergic transmitter is free NO, and the possibility that another compound is acting as mediator still remains open.

British Journal of Pharmacology (2000) 129, 53–62; doi:10.1038/sj.bjp.0703000
Biphasic effects of NMDA on the motility of the rat portal vein
Authors: Rossetti Z L , Mameli M , Vargiu R , Fadda F , Mancinelli R 
Published: January 2005

The effect of NMDA on the motility of the rat portal vein was studied in an isolated preparation. NMDA induced a concentration‐dependent (10−7–10−4 M) increase of the contraction frequency (maximum increase, 148±6% of control at NMDA 10−4 M).
The NMDA‐induced excitatory response was prevented by the competitive NMDA receptor antagonists (±)‐2‐Amino‐5‐phosphonopentanoic acid (AP‐5, 5×10−4 M) or (RS)‐3‐(2‐carboxypiperazine‐4‐yl) propyl‐1‐phosphonic acid (CPP, 10−4 M).
Tetrodotoxin (TTX, 10−6 M) or atropine (10−4 M) abolished the NMDA‐induced increase of the portal vein motility and reversed the excitatory effect to a concentration‐dependent inhibition (maximum inhibition, 52±8 and 29±7% of controls, respectively, at NMDA 10−3 M).
Removal of the endothelium abolished the NMDA‐induced inhibitory response. Sodium nitroprusside concentration‐dependently (10−7–10−5 M) inhibited the portal vein motility, while L‐NG‐nitro‐arginine methyl ester (L‐NAME, 10−4 M) reversed the inhibitory effect of NMDA (in the presence of TTX), restoring the portal vein spontaneous activity to control values.
These results show that NMDA modulates the portal vein motility in a biphasic manner: via indirect activation, through prejunctional NMDA receptors presumably located on intrinsic excitatory neuronal afferences, or via direct inhibition, through endothelial NMDA receptors activating the nitric oxide pathway. Overall these findings support the hypothesis of the existence of a peripheral glutamatergic innervation modulating the contractile activity of the rat portal vein.

British Journal of Pharmacology (2000) 129, 156–162; doi:10.1038/sj.bjp.0703002
Bradyzide, a potent non‐peptide B2 bradykinin receptor antagonist with long‐lasting oral activity in animal models of inflammatory hyperalgesia
Authors: Burgess Gillian M , Perkins Martin N , Rang Humphrey P , Campbell Elizabeth A , Brown Michael C , McIntyre Peter , Urban Laszlo , Dziadulewicz Edward K , Ritchie Timothy J , Hallett Allan , Snell Christopher R , Wrigglesworth Roger , Lee Wai , Davis Clare , Phagoo Steve B , Davis Andrew J , Phillips Elsa , Drake Gillian S , Hughes Glyn A , Dunstan Andrew , Bloomfield Graham C 
Published: January 2005

Bradyzide is from a novel class of rodent‐selective non‐peptide B2 bradykinin antagonists (1‐(2‐Nitrophenyl)thiosemicarbazides).
Bradyzide has high affinity for the rodent B2 receptor, displacing [3H]‐bradykinin binding in NG108‐15 cells and in Cos‐7 cells expressing the rat receptor with KI values of 0.51±0.18 nM (n=3) and 0.89±0.27 nM (n=3), respectively.
Bradyzide is a competitive antagonist, inhibiting B2 receptor‐induced 45Ca efflux from NG108‐15 cells with a pKB of 8.0±0.16 (n=5) and a Schild slope of 1.05.
In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin‐induced ventral root depolarizations (IC50 value; 1.6±0.05 nM (n=3)).
Bradyzide is much less potent at the human than at the rodent B2 receptor, displacing [3H]‐bradykinin binding in human fibroblasts and in Cos‐7 cells expressing the human B2 receptor with KI values of 393±90 nM (n=3) and 772±144 nM (n=3), respectively. Bradyzide inhibits bradykinin‐induced [3H]‐inositol trisphosphate (IP3) formation with IC50 values of 11.6±1.4 nM (n=3) at the rat and 2.4±0.3 μM (n=3) at the human receptor.
Bradyzide does not interact with a range of other receptors, including human and rat B1 bradykinin receptors.
Bradyzide is orally available and blocks bradykinin‐induced hypotension and plasma extravasation.
Bradyzide shows long‐lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)‐induced mechanical hyperalgesia in the rat knee joint (ED50, 0.84 μmol kg−1; duration of action >4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non‐steroidal anti‐inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days.
In summary, bradyzide is a potent, orally active, antagonist of the B2 bradykinin receptor, with selectivity for the rodent over the human receptor.

British Journal of Pharmacology (2000) 129, 77–86; doi:10.1038/sj.bjp.0703012
Antagonism of calcium currents and neurotransmitter release by barium ions at frog motor nerve endings
Authors: Silinsky Eugene M 
Published: January 2005

The effects of Ba2+ (0.1–2 mM) on the component of the perineural voltage change associated with nerve terminal calcium currents (prejunctional Ca2+ currents) were compared with the effects of this ion to antagonize calcium‐dependent acetylcholine (ACh) release. These experiments were made on isolated neuromuscular junctions of the frog.
In the presence of sufficient concentrations of K+ channel blockers to eliminate measurable prejunctional K+ currents, low concentrations of Ba2+ selectively antagonized prejunctional Ca2+ currents in normal Ca2+ solutions. Higher concentrations of Ba2+ also substantially reduced the Na+ component of the perineural waveform.
Ba2+ inhibited the prolonged prejunctional Ca2+ currents that developed in the presence of higher concentrations of K+ channel blockers.
Simultaneous measurements of the prejunctional Ca2+ currents and the electrophysiological correlates of ACh release (i.e. end‐plate potentials, EPPs) were made under conditions of modest K+ channel blockade. Under these conditions, Ba2+ generally produced simultaneous decreases in both Ca2+ currents and EPP amplitudes. In some instances, a prolongation of prejunctional Ca2+ currents and a transient increase in EPP amplitudes preceded the decreases in both electrophysiological events.
These results suggest that Ba2+ ions can antagonize the entry of calcium into motor nerve endings and this effect is likely to be responsible for the inhibitory effects of Ba2+ on evoked ACh release.

British Journal of Pharmacology (2000) 129, 360–366; doi:10.1038/sj.bjp.0703036