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PubMed1996

Conotoxin-sensitive and conotoxin-resistant Ca2+ currents in fish retinal ganglion cells.

Using whole-cell patch-clamp methods, we tested whether omega-toxins from Conus block voltage-gated Ca2+ currents in teleost central neurons. The fractions omega-CTx-GVIA and omega-CTx-MVIIC, together with omega-toxins from Agelenopsis, the dihydropyridine BAY-K-8644, and voltage steps, produced effects indicating three types of Ca2+ current in dissociated goldfish retinal ganglion cells. One was activated by depolarization of most cells beyond -65 mV, primed at -95 mV but not at -45 mV, reduced by Ni2+, and unchanged by conotoxins, agatoxins, or BAY-K-8644. The second type constituted more than three-quarters of the total Ca2+ current in all cells, and at test potentials more positive than -30 mV, was reduced consistently by omega-CTx-GVIA, omega-CTx-MVIIC, and omega-Aga-IA, but not omega-Aga-IVA. The third Ca2+ current type was augmented by BAY-K-8644 at test potentials as negative as -45 mV, even in the presence of omega-CTx-GVIA. Replacement of extracellular Ca2+ by Ba2+ augmented current amplitude and slowed current decay. Conditioning depolarizations reduced Ca2+ current amplitude less than did omega-CTx-GVIA, and slowed current decay to imperceptible rates. These results provide the first description of conotoxin-sensitive, voltage-gated Ca2+ current recorded from teleost central neurons. Although most of the high-threshold Ca2+ current in these cells is blocked by omega-CTx-GVIA, it is also Ni(2+)-sensitive, and relatively resistant to omega-Aga-IIIA. The voltage sensitivities of low-and high-threshold Ca2+ current may suit current recruitment in situ after light-evoked hyperpolarizations end, and after light-evoked depolarizations begin, respectively.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel.

We determined the structure in solution by (1)H two-dimensional NMR of Maurocalcine from the venom of Scorpio maurus. This toxin has been demonstrated to be a potent effector of ryanodyne-sensitive calcium channel from skeletal muscles. This is the first description of a scorpion toxin which folds following the Inhibitor Cystine Knot fold (ICK) already described for numerous toxic and inhibitory peptides, as well as for various protease inhibitors. Its three dimensional structure consists of a compact disulfide-bonded core from which emerge loops and the N-terminus. A double-stranded antiparallel beta-sheet comprises residues 20-23 and 30-33. A third extended strand (residues 9-11) is perpendicular to the beta-sheet. Maurocalcine structure mimics the activating segment of the dihydropyridine receptor II-III loop and is therefore potentially useful for dihydropyridine receptor/ryanodine receptor interaction studies. Proteins 2000;40:436-442.

Amino Acid Sequence↗
PubMed1988

Epidermal growth factor-stimulated DNA synthesis requires an influx of extracellular calcium.

The dependency of normal cell proliferation on adequate extracellular Ca2+ levels was further investigated by determining the role of Ca2+ influx in epidermal growth factor (EGF)-induced rat liver epithelial (T51B) cell DNA synthesis. Fura-2-loaded T51B cells responded with an increase in [Ca2+]i to EGF (5-50 ng/ml) that was blocked by low (25 microM) extracellular Ca2+ or by pretreatment with 50 microM La3+ to inhibit plasma membrane Ca2+ flux. Confluent T51B cells treated for 24 h with EGF (0.1-50 ng/ml) dose-dependently incorporated [3H]-thymidine into cell nuclei. Low extracellular Ca2+ or addition of La3+ prevented the EGF-stimulated rise in labeled nuclei, indicating that a movement of Ca2+ into the cell was required for DNA synthesis. This was supported by our findings that bradykinin, which induced a rise in [Ca2+]i by opening plasma membrane Ca2+ channels in T51B cells (but not A23187, thrombin or ATP, which raise [Ca2+]i primary through mobilization of intracellular Ca2+ stores), potentiated DNA synthesis stimulated by submaximal doses of EGF. Potentiation of the action of EGF by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), indicates that activation of protein kinase C and an influx of Ca2+ share a common mechanism for initiating DNA synthesis.

Animals↗
PubMed1993

Design of a functional calcium channel protein: inferences about an ion channel-forming motif derived from the primary structure of voltage-gated calcium channels.

To identify sequence-specific motifs associated with the formation of an ionic pore, we systematically evaluated the channel-forming activity of synthetic peptides with sequence of predicted transmembrane segments of the voltage-gated calcium channel. The amino acid sequence of voltage-gated, dihydropyridine (DHP)-sensitive calcium channels suggests the presence in each of four homologous repeats (I-IV) of six segments (S1-S6) predicted to form membrane-spanning, alpha-helical structures. Only peptides representing amphipathic segments S2 or S3 form channels in lipid bilayers. To generate a functional calcium channel based on a four-helix bundle motif, four-helix bundle proteins representing IVS2 (T4CaIVS2) or IVS3 (T4CaIVS3) were synthesized. Both proteins form cation-selective channels, but with distinct characteristics: the single-channel conductance in 50 mM BaCl2 is 3 pS and 10 pS. For T4CaIVS3, the conductance saturates with increasing concentration of divalent cation. The dissociation constants for Ba2+, Ca2+, and Sr2+ are 13.6 mM, 17.7 mM, and 15.0 mM, respectively. The conductance of T4CaIVS2 does not saturate up to 150 mM salt. Whereas T4CaIVS3 is blocked by microM Ca2+ and Cd2+, T4CaIVS2 is not blocked by divalent cations. Only T4CaIVS3 is modulated by enantiomers of the DHP derivative BayK 8644, demonstrating sequence requirement for specific drug action. Thus, only T4CaIVS3 exhibits pore properties characteristic also of authentic calcium channels. The designed functional calcium channel may provide insights into fundamental mechanisms of ionic permeation and drug action, information that may in turn further our understanding of molecular determinants underlying authentic pore structures.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Activin A and all-trans-retinoic acid cooperatively enhanced the functional activity of L-type Ca2+ channels in the neuroblastoma C1300 cell line.

Activin, a member of the transforming growth factor-beta superfamily, regulates various physiological functions. In the present study, we investigated the effect of activin on neuronal differentiation, particularly the functional activity of voltage-dependent Ca2+ channels, in murine neuroblastoma C1300 cells. A slight K(+)-induced increase in the intracellular free Ca2+ ([Ca2+]i) was observed in C1300 cells untreated and treated with either activin A or all-trans-retinoic acid, while treatment with both agents significantly enhanced the increase. The [Ca2+]i increases potentiated by activin A and all-trans-retinoic acid were nearly abolished in the presence of 1.0 mM nickel or in the absence of extracellular Ca2+. Nifedipine (0.1 microM) and omega-conotoxin (1.0 microM), inhibitors of L- and N-type Ca2+ channels, respectively, partially inhibited these responses, however the inhibitory effects of these compounds were not additive. In addition, Bay K 8644, an activator of L-type Ca2+ channels, enhanced the K(+)-induced [Ca2+]i increase. These findings indicated that depolarization evoked the Ca2+ influx, at least in part, through L-type Ca2+ channels in C1300 cells treated with both activin A and all-trans-retinoic acid.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats.

The present study was undertaken to determine whether altered expression of the VDCC beta-subunits in pancreatic beta-cells could play a role in the changes in beta-cell sensitivity to glucose that occur with diabetes. Application of competitive RT-PCR procedure revealed that in normal Wistar rats, LETO and prediabetic OLETF rats, the beta(2)-subunit mRNA levels were 60-200-fold greater than the levels for the beta(3)-subunit. These findings suggest that the beta(2)-subunit as well as the beta-cell type VDCC1 alpha(1)-subunit may be the predominant form of the VDCC expressed in pancreatic beta-cells. The levels of mRNA encoding the beta-subunits and the beta-cell type alpha(1)-subunit as well as insulin were significantly reduced in diabetic rats. Perfusion experiments revealed that diabetic rats showed the higher basal insulin secretion and profoundly impaired insulin secretory responses to glucose compared with non-diabetic rats. Alternatively, impaired insulin secretory responses to glucose in high dose glucose-infused rats were recovered partly with the elevation of mRNA levels of the VDCC beta(2)- and beta(3)-subunits as well as the alpha(1)-subunit by the treatment with diazoxide. Thus, considering the possibility that the most striking effect of the VDCC alpha(1) beta-subunit coexpression in pancreatic beta-cells might occur on activation kinetics like the skeletal muscle, the impairment of further activation of the VDCCs to acute glucose challenge caused by the reduced expressions of the alpha(1) beta-subunits mRNAs in type 2 diabetic animals might be at least partly associated with the alterations in beta-cell sensitivity to glucose.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Potassium current oscillations across the rabbit lens epithelium.

Rabbit lenses expressing spontaneous oscillations in translens short-circuit current (Isc) are obtained somewhat frequently, with this phenomenon observed in approximately 30% of isolated lenses as described earlier (Exp. Eye Res. 61, 129-140, 1995). Since pharmacological protocols to consistently elicit Isc oscillations were not found, characterizations of the underlying transport processes have been limited to the application of various inhibitors on the spontaneous phenomenon. The present report extends the initial observations by confirming that oscillations are immediately inhibited upon the anterior addition of the Ca2+ channel blocker nifedipine (10 microM), and by demonstrating that other treatments which should affect epithelial Ca2+ homeostasis are also inhibitory (e.g., Bay K 8644 (10 microM), diltiazem (10 microM), EGTA (2 mm), and Ca2+-free media). Furthermore, Isc oscillations are immediately inhibited by the K+ channel blocker, Ba2+, but not by the Na+-K+ pump inhibitor, ouabain. The intracellular Ca2+ mobilizing agents thapsigargin (0.1 microM) or acetylcholine (1 microM) modified but did not permanently inhibit the oscillations, confirming earlier observations. At 50 microM, however, acetylcholine addition was inhibitory, but reversible, for oscillations restarted upon its subsequent removal. In addition, lens oscillations were also characterized under open-circuit conditions with microelectrodes inserted in the superficial cells near the equator of lenses isolated in a divided chamber. The potential difference (PD) across each lens face was recorded, as was the translens PD (PDt), which equals the difference between the PDs across each lens surface. Oscillations in PDt were obtained in 7 of 26 lenses. The oscillations arose only from an oscillation in the PD across the anterior face (PDa). While PDa and PDt oscillated with the same amplitude (approximately 12 mV) and period (approximately 70 sec), the PD across the posterior surface remained stable. During these oscillations the conductance of the anterior surface was maximal at the most positive voltage of the anterior bath with respect to the lens interior (46 mV), whereas, minimal conductance occurred at the least positive PDa (34 mV). Overall, these observations are consistent with the likely presence of voltage-operated Ca2+ channels in parallel with various Ca2+-sensitive K+ channels in the epithelial basolateral membrane. A model to explain the oscillatory pattern across the anterior face while the PD across the posterior face remains unaltered is presented.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Molecular level model for the agonist/antagonist selectivity of the 1,4-dihydropyridine calcium channel receptor.

Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxy lat e], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5- carboxylate], and Bay O 9507 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(4-nitrophenyl)-pyridine-5-carboxy lat e] were determined. The conformations of the 1,4-DHP rings of these activator analogues of Bay K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate] do not suggest that their activator properties are as strongly correlated with the degree of 1,4-DHP ring flattening as was indicated for members of the corresponding antagonist series. The solid state hydrogen bonding of the N(1)-H groups of the activators is not, unlike that of their antagonist counterparts, to acceptors that are directly in line with the donor. Rather, acceptor groups are positioned within +/- 60 degrees of the N(1)-H bond in the vertical plane of the 1,4-DHP ring. Previously determined structure-activity relationships have indicated the importance of this N(1)-H group to the activity of the 1,4-DHP antagonists. Based on these observations, a model is advanced to describe the 1,4-DHP binding site of the voltage-gated Ca2+ channel and its ability to accommodate both antagonist and activator ligands.

Calcium Channel Agonists↗
PubMed1995

Enhancement of Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells by phorbol esters with and without activation of protein kinase C.

The effects of phorbol esters on Ca2+ channel currents in human neuroblastoma SH-SY5Y cells were studied using whole-cell patch-clamp recordings. Bath application of 12-O-tetradecanoylphorbol-13-acetate (TPA) or phorbol 12,13-dibutyrate (PDBu; 100 nM to 1 microM), known activators of protein kinase C (PKC), enhanced Ca2+ channel currents in a voltage-dependent manner similar to that of Bay K 8644. TPA also enhanced Ca2+ channel currents during cell dialysis with the PKC pseudosubstrate, PKC(19-36), and in cells which had been pre-incubated with 500 nM staurosporine, and which were exposed to staurosporine during recordings. Application of 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD; 100 nM), which does not activate PKC, caused current enhancement similar to the effects of TPA. However, intracellular dialysis of TPA was without effect on Ca2+ channel currents. Residual Ca2+ channel currents recorded after exposure to 1 microM omega-conotoxin GVIA were still enhanced by TPA, but in the presence of either Bay K 8644 (5 microM) or nifedipine (5 microM), TPA was without effect. When cells were pre-incubated for 10 min at 37 degrees C with 100 nM TPA, currents subsequently recorded in its absence were enhanced as compared to untreated cells; 5 microM nifedipine still inhibited currents to the same degree. This enhancement was not mimicked by 4 alpha-PDD, and was inhibited by staurosporine. Our results indicate that acute applications of phorbol esters (at concentrations commonly used to activate PKC) enhance L-type Ca2+ channel currents in SH-SY5Y cells via a PKC-independent mechanism which appears similar to that induced by Bay K 8644. By contrast, pre-incubation with TPA enhances both L- and N-type currents via activation of PKC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Differential regulation of cytosolic calcium between afferent arteriol ar smooth muscle cells from mouse kidney.

Using a combination of whole-cell patch-clamping and calcium microspectrofluorimetry we have examined the calcium regulation and calcium-activated electrical currents in smooth muscle cells along mouse renal afferent arterioles. In cells located at a distance up to 50microm from the glomerular vascular pole, guanosine 5'-[gamma-thio]triphosphate, (GTP[tau -S], 100micromol/l) and angiotensin II (1micromol/l) evoked internal calcium mobilization and oscillations of intracellular calcium concentration. Membrane depolarization up to +30mV did not increase cytosolic free calcium in these cells, which displayed calcium-activated chloride currents. In cells located more distant than 100microm from the glomerular vascular pole, GTP[tau -S] did not increase cytosolic calcium at negative membrane potentials. Depolarization of these cells to 0mV or positive membrane potentials increased intracellular calcium in a dihydropyridine-sensitive manner. These cells responded to angiotensin II with single calcium transients and also displayed calcium-activated chloride currents. These findings suggest that intracellular calcium is differentially regulated between afferent arteriolar smooth muscle cells from mouse kidney: in smooth muscle cells which are distant from the glomerular vascular pole, cytosolic calcium is increased primarily via calcium influx through potential-operated calcium channels, whilst in cells which are close to the vascular pole intracellular calcium is elevated predominantly via mobilization from internal stores. Both cell types are equipped with receptors for angiotensin II and possess calcium-activated chloride channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytes in vitro.

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studied in vitro. [3H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10(-4) M-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose dependent fashion with ED50 value of 2.4 x 10(-5) M. Unexpectedly, CGP 28392 (10(-4) M-10(-7) M) acts as a calcium entry blocker and produces a strong inhibitory effect on lymphocyte proliferation (ED50-2 x 10(-5) M). BAY K 8644 at a high concentration (10(-4) M) also has an inhibitory effect but at a lower concentration (10(-6) M-10(-10) M) significantly increased [3H]-thymidine uptake and abolished the inhibitory effect of nimodipine. This effect of nimodipine was also reversed by 5 x 10(-3) M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytes in vitro.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Low-conductivity calcium channels in the macrophage plasma membrane: activation by inositol-1,4,5-triphosphate.

Local voltage clamping was applied to mouse macrophage plasma membrane to study calcium channels activated by inositol-1,4,5-triphosphate (IP3) and blocked by heparin. These channels were clearly distinguished from IP3-activated channels of the endoplasmic reticulum by their low conductivity (about 1 pSm for 100 mM Ca2+), high selectivity for Ca2+ relative to K+ (P(Ca):P(K) > 1000), calcium inactivation, and activation on hyperpolarization; these properties allowed them to be assigned to the I(CRAC) family. On the other hand, the properties of the IP3 receptors of these channels (IP3R), i.e., the dose-dependent effect of IP3, the IP3 desensitization of the receptor, and the sensitivity to micromolar concentrations of heparin and arachidonic acid were close to those of the endoplasmic reticulum IP3 receptor. The most likely interpretation of these data is that IP3R are not located in the endoplasmic reticulum, but, acting via some kind of conformational change occurring on binding of IP3, transmit a signal from the endoplasmic reticulum to the highly selective Ca2+ channels. This point of view is in agreement with the published "coupling model" [1].

Animals↗
PubMed1994

Identification of the Ca2+ current activated by vasoconstrictors in vascular smooth muscle cells.

The noncontractile aortic cell line A7r5 was chosen to study the effect of the vasoconstrictor peptide vasopressin on transmembrane Ca2+ movements, using conventional whole-cell patch recording techniques. Conditions in which previously characterised vasoconstrictor-modulated currents were suppressed revealed a tiny inward current component (-18 +/- 2 pA, n = 50, at -61 mV in 110 mM CaCl2). The vasopressin-activated inward current was absent when Ca2+ was absent from the extracellular solution, and the current amplitude increased with [Ca2+] (0.01-110 mM), with an apparent dissociation constant for Ca2+ of 9.7 mM. It was highly selective for Ca2+ over monovalent cations (permeability ratio Ca/Cs greater than 17). It was not voltage gated, except that the current/potential characteristic showed some inwards rectification. Amplitudes of the evoked inward currents had the same order of magnitude in Sr2+ and Ca2+, whereas they were much smaller in Mn2+, suggesting that this pathway is highly permeable to Sr2+ but poorly permeable to Mn2+. Inward currents evoked in Ca2+ were inhibited by other cations with the following order of potency: La3+ > Cd2+ > Co2+ approximately Ni2+ approximately Mn2+. The channel producing this current corresponds most probably to the ionic pathway originally called the receptor-operated calcium channel, which produces a long-lasting, constrictor-induced plateau of increased intracellular free calcium concentration in smooth muscle.

Animals↗
PubMed1997

The contribution of different types of calcium channels to electrically-evoked adenosine release from rat hippocampal slices.

The role of L-, N- and P-type voltage-dependent calcium channels (VDCCs) in the release of adenosine from rat hippocampal slices was investigated by evaluating the effect of the L-channel activator 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyr idi ne carboxylic acid methyl ester (Bay K 8644) and of three calcium channel antagonists: the L-channel antagonist nifedipine, the N-channel blocker omega-conotoxin GVIA (omega-CgTx) and the P-channel blocker omega-agatoxin IVA (omega-Aga-IVA). Adenosine and inosine release, evoked by 5 min electrical stimulation at 10 Hz of hippocampal slices, was assayed by HPLC with ultraviolet absorbance or fluorimetric detection. Nifedipine (100 nM) did not affect adenosine and inosine release evoked by electrical stimulation. Bay K 8644 (100 nM) brought about a statistically significant increase in adenosine evoked release (70%). At a higher concentration (1 microM) Bay K 8644 had no significant effect either on adenosine or inosine release evoked by electrical stimulation. The increase in adenosine release elicited by 100 nM Bay K 8644 was abolished by nifedipine (100 nM). Both omega-CgTx (10 microM) and omega-Aga-IVA (200 nM) caused a statistically significant reduction (77-78%) in evoked release of adenosine. When the previously demonstrated glutamate-dependent component of the release of adenosine was suppressed in the presence of the NMDA and non-NMDA receptor antagonists, D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7. 100 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), the remaining release of adenosine was again significantly reduced by omega-CgTx (10 microM) (60%) and omega-Aga-IVA (200 nM) (73%). These data suggest that, while L-type VDCCs are involved in the regulation of the evoked release of adenosine only when activated by Bay K 8644, both P- and N-channels play a direct role in the calcium entry involved in the coupling process between electrical stimulation and adenosine release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Multiple calcium channels are required for pituitary adenylate cyclase-activating polypeptide-induced catecholamine secretion from bovine cultured adrenal chromaffin cells.

The effects of L-, N-, P- and Q-type calcium channel antagonists and (+/-)-BayK-8644 on catecholamine release induced by pituitary adenylate cyclase-activating polypeptide (PACAP-27) were investigated in bovine cultured adrenal chromaffin cells. PACAP-27 induced the release of 4-15% of the total cellular catecholamines over 7 min, with an EC50 of 20 nM and the effect approaching maximum at 100 nM. Catecholamine release was fully dependent on the presence of extracellular calcium. The dihydropyridine nitrendipine which inhibits L-type calcium channels inhibited PACAP-27-induced secretion in a concentration dependent manner with an inhibition of 20-30% at 1 microM. In contrast, (+/-)-BayK-8644, which prolongs the opening of L-type calcium channels produced a concentration-dependent increase in PACAP-27-induced catecholamine release with 1 microM increasing release by 40-60%. Blockade of N-type calcium channels with omega-conotoxin GVIA reduced release by 5-15%. Block of P-type channels with low concentrations of omega-agatoxin IVA (< or = 30 nM) had no significant effect on release, while higher concentrations (100-300 nM) which block Q-type channels reduced release by up to 15%. omega-Conotoxin MVIIC, an antagonist of Q-type calcium channels and also of N- and P-type channels, inhibited release in a concentration-dependent manner with a near maximum effect of 30-50% produced by 300 nM. The combination of omega-conotoxin GVIA and omega-agatoxin IVA reduced release by 40-50%. Addition of omega-conotoxin MVIIC (300 nM) to the combination of omega-conotoxin GVIA (10 nM) and omega-agatoxin IVA (100 nM) did not inhibit catecholamine release more than with omega-conotoxin GVIA and omega-agatoxin IVA alone, indicating that 100 nM omega-agatoxin IVA was sufficient to block the Q-type calcium channels. When nitrendipine was used together with omega-conotoxin GVIA, omega-agatoxin IVA and omega-conotoxin MVIIC, catecholamine release induced by 20 nM or 100 nM PACAP-27 was reduced by 70-85%. Taken together these results suggest that influx of calcium through multiple different voltage-sensitive calcium channels mediate PACAP-27-induced catecholamine release from bovine chromaffin cells, and that L-, N- and Q-channels contribute to this response.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗