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Results for “Calcium Channel Agonists”

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At least 19 recordsLinked to original sources

PubMed1992

Interaction of U-50,488H with calcium channel agonists and antagonists in different cardiac tissues.

1. The present study examined the interaction of U-50,488H (specific k-agonist) with diltiazem (calcium channel antagonist) or Bay K 8644 (calcium channel agonist) on isolated left and right atria of the rat. 2. The inhibitory effects of U-50,488H on left and right atria were unaffected by the k-receptor antagonist MR-2266 (10(-7) and 5 x 10(-7) M) suggesting that they were not mediated via opioid receptors. 3. The inhibitory cardiac effects induced by U-50,488H were antagonized in presence of Bay K 8644. The negative inotropic response to the maximum concentration of U-50,488H used in presence of two concentrations of Bay K 8644 (10(-9), 3 x 10(-9) M) were 19 +/- 0.9% and 9 +/- 0.1% reductions in contractility respectively. These values were significantly (P < 0.001) lower than that obtained with the k-agonist alone (76 +/- 3.6%). Similar results were obtained for the negative chronotropism of right atria. 4. The inhibitory effect of U-50,488H was potentiating in the presence of diltiazem (5 x 10(-8) or 10(-7) M). The IC50 values for U-50,488H obtained in the left (22 +/- 2 x 10(-6) M) and right atria (610 +/- 40 x 10(-6) M) were significantly (P < 0.001) decreased in the presence of diltiazem. 5. These data demonstrate that transmembrane calcium influx may play an important role in the inhibitory cardiac effects of U-50,488H, which may be independent of k-receptor stimulation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1987

Induction of seizures in mice by intracerebroventricular administration of the calcium channel agonist BAY k 8644.

The calcium channel agonist BAY k 8644 was used to investigate the role of the calcium ion (Ca2+) in epileptogenesis. Intracerebroventricular administration of the compound induced murine seizures that were reversed by calcium channel inhibitors (CCIs) but not by anticonvulsants such as carbamazepine, pentobarbital, and diazepam. The seizures were exacerbated by phenytoin and valproic acid. Chronic administration of CCI's, previously shown to produce down-regulation of the binding of the CCI [3H]nitrendipine, resulted in augmentation of BAY k 8644-induced seizures.

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

PubMed1992

Will the calcium channel agonist BAY K8644 inhibit halothane-induced impairment of calcium current?

The inhaled anesthetics impair transsarcolemmal calcium entry (ICa) in myocardial cells, although the mechanism of this interaction is not known. This inhibition of calcium entry has been implicated in the myocardial depression of the volatile anesthetics. To further characterize this interaction and to evaluate whether a calcium channel agonist could attenuate or prevent the inhibition of calcium entry, the effect of the calcium channel agonist BAY K8644 on the impairment of ICa by halothane was evaluated in single guinea pig ventricular myocytes. Calcium currents were evoked by means of the whole-cell voltage-clamp technique. Baseline peak ICa was higher in the cells exposed to 5 microM BAY K8644 (311 vs 206 pA/cm2, P less than 0.04). On exposure to 1% halothane, peak ICa was impaired to an identical degree whether or not cells were exposed to BAY K8644 (78% and 79% of baseline value). This is consistent with the suggestion that the effects of these agents on ICa are nonspecific. However, the increase in ICa suggests that appropriate calcium channel agonists might serve to ameliorate the myocardial depressant effects of halothane.

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

PubMed1986

Exaggerated Dahl salt-sensitive kidney response to calcium channel agonist isomer of Bay k 8644, but not to calcium channel antagonist isomer of Bay k 8644.

We examined the influence of calcium channel agonist and antagonist optical isomers of BAY-K-8644 on the renal vascular resistance, glomerular filtration rate and sodium excretion of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistance (DR) rats previously stabilized on high- and low-NaCl regimens. The agonist isomer affected these parameters at a lower concentration and to a greater degree in the high-salt DS rat kidneys than in the other three groups. The antagonist isomer also reversed agonist-induced changes to the greatest degree in the high-salt DS rat kidneys. However, the low-salt DS and high-salt DR rat kidneys appeared to be slightly more reactive to these isomers than the low-salt DR rat kidneys, suggesting that hereditary predisposition and dietary NaCl may contribute independently to renal responsiveness to calcium channel-active agents.

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

PubMed1988

Calcium channel agonists and antagonists: effects of chronic treatment on pituitary prolactin synthesis and intracellular calcium.

PRL synthesis by GH cells in culture has previously been shown to increase when calcium is added to cultures grown in calcium-depleted medium or when cultures are treated for 18 h or longer with the dihydropyridine calcium channel agonist BAY K8644, whereas the antagonist nimodipine inhibits PRL. The experiments described here were designed to test whether differences in PRL synthesis caused by the dihydropyridines are due to changes in PRL mRNA levels, whether structurally different classes of calcium channel blockers alter PRL production, and whether long term treatment with calcium channel agonists and antagonists alters intracellular free calcium, [Ca2+]i. PRL synthesis and PRL mRNA levels were increased similarly by BAY K8644 and decreased in parallel by the dihydropyridine antagonist nimodipine, while overall protein and RNA synthesis were not changed by either the agonist or antagonist. Two calcium channel blockers which act at different sites on L-type channels than the dihydropyridines also inhibited PRL synthesis without affecting GH; 5 microM verapamil reduced PRL by 64% and 15 microM diltiazem by 89%. Partial depolarization with 5-25 mM KCl increased PRL synthesis up to 2-fold. The intracellular free calcium ion concentration was estimated by Quin 2 and averaged 142 nM for control cultures in normal medium, and 128 and 168 nM for cultures treated 72 h with nimodipine or BAY K8644, respectively. Nimodipine totally prevented the calcium rise obtained upon depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

BAY-K-8644, a calcium channel agonist, induces a rise in cytoplasmic free calcium and iodide discharge in thyroid cells.

BAY-K-8644, a calcium channel agonist, induces a rise in cytoplasmic free calcium and iodide discharge in cultured porcine thyroid cells. The cytoplasmic free calcium concentration, [Ca2+]i, was measured using aequorin, a calcium-sensitive photoprotein. BAY-K-8644, a dihydropyridine derivative, acts as a Ca channel agonist and induces a rise in [Ca2+]i and iodide discharge; 0.5 nM BAY-K-8644 is a minimal dose to effect a rise in [Ca2+]i and iodide discharge and 50 nM BAY-K-8644 produces the maximal effect. The data indicate that BAY-K-8644-induced iodide discharge is mediated by a rise in [Ca2+]i.

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

PubMed1990

RS 30026: a potent and effective calcium channel agonist.

1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked. 5. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 nm Bay K 8644, with a much smaller shift in the presence of 500nm Bay K 8644. RS 30026 (100 and 500nM) caused concentration-dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. 6. RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

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

PubMed1991

(+)-S-12967 and (-)-S-12968: 1,4-dihydropyridine stereoisomers with calcium channel agonistic and antagonistic properties in rat resistance arteries.

1. The actions of (+)-S-12967 and (-)-S-12968 two isomers of a new 1,4-dihydropyridine (DHP) derivative, were studied on 125 mM K(+)-, Ca(2+)- and noradrenaline-induced contractions in rat isolated mesenteric resistance arteries and compared to those of nifedipine. 2. The action of (+)-S-12967 and (-)-S-12968 was slow in onset in contrast to nifedipine. Both isomers had a dual contractile and relaxant action in arteries contracted with 125 mM K+; however, the (-)-isomer was about 300 times more potent than the (+)-isomer. The response to 125 mM K+, being depressed by 70%, recovered within 20 to 30 min for all DHP derivatives. All vessels were treated with 1 x 10(-6) M phenoxybenzamine thus excluding the possibility that the contraction is mediated by activation of amine-receptors. 3. Both (+)-S-12967 and (-)-S-12968 at low concentrations potentiated responses induced by Ca2+ in arteries activated by 125 mM K+ and inhibited the responses at higher concentrations. (+)-S-12967 and (-)-S-12968 had no contractile action in arteries kept in normal buffer. Nifedipine had only an inhibitory action on vessel responses to 125 mM K+ and Ca2+. 4. Both isomers and nifedipine depressed the maximal vessel response to noradrenaline by about 20% and 44%, respectively. 5. The results confirm that DHP calcium antagonists selectively inhibit vascular smooth muscle responses induced by high potassium and that the potency of 1,4-DHP isomers may vary considerably. Furthermore, since the agonistic/antagonistic properties on the calcium channel were shared by both stereoisomers of the 1,4-DHP molecule and apparently dependent on their concentration and the vascular smooth muscle membrane potential, it suggests that the agonistic action of 1,4-DHPs may be ascribed to functional characteristics of their binding site regulating the Ca2l -channel.

Animals↗

PubMed1988

Increased vascular response to calcium channel agonist by Dahl S rat kidney.

We examined responses to the calcium channel agonist, BAY-K 8644, of isolated perfused kidneys from Dahl salt-sensitive (DS) and -resistant (DR) rats that had been stabilized on high (HI) and low (LO) NaCl intakes. Mean arterial pressures of DS/HI rats exceeded those of the other three groups. BAY-K 8644 significantly increased the renal vascular resistance (RVR) of DS/HI and DS/LO kidneys, by 38 and 12%, respectively, but did not increase RVR of DR/HI or DR/LO kidneys significantly (6 and 2%, respectively). Increases in RVR and decreases in glomerular filtration rate of DS/HI kidneys exceeded those of DR/HI kidneys. Increases in the RVR of DS/LO kidneys exceeded those of DR/LO kidneys. Experiments utilizing the separate calcium channel agonist and antagonist enantiomers of BAY-K 8644 corroborated these findings, but at lower concentrations. "Chemical sympathectomy" with 6-hydroxydopamine increased the reactivity of kidneys from only high-NaCl animals to BAY-K 8644 without regard to Dahl S or R status. In conclusion, the DS kidney vasculature manifests an increase in responsiveness to this calcium channel agonist, independently of antecedent NaCl loading or high blood pressure. However, a high antecedent salt intake or hypertension enhances vascular responsiveness of the DS kidney to BAY-K 8644.

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

PubMed1987

Evidence for distinct calcium channel agonist and antagonist binding sites in intact cultured embryonic chick ventricular cells.

To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular cells. Equilibrium binding studies using the antagonist (+)-[3H]PN200-110 demonstrated equilibrium binding to intact, beating cells consistent with a single class of binding sites (KD, 1.1 nM; Bmax, 40 fmol/mg protein). Membrane depolarization of the intact cells by incubation in 30 mM potassium caused a 91% increase in the apparent number of (+)-PN200-110 binding sites (Bmax 76 fmol/mg protein), but no significant change in the KD (1.2 nM). The (+)-PN200-110 produced a concentration-dependent decrease in calcium uptake (IC50 2.2 nM) and contractile amplitude (IC50 5.6 nM). The calcium channel agonist, (+/-)-[3H]BAY k 8644, bound to two distinct binding sites with high affinity (KD 1.0 nM) and low affinity (KD 1.9 microM). The (+/-)-BAY k 8644 produced biphasic modulation of calcium flux and contractile state. At concentrations of 100 nM or less, (+/-)-BAY k 8644 increased calcium flux and contractile amplitude, consistent with drug interaction with the high affinity agonist site. However, at higher concentrations, the stimulatory effect of (+/-)-BAY k 8644 on calcium flux and contractile amplitude was abolished, a finding that is consistent with drug interaction with the low affinity antagonist site.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1985

Calcium channel agonist BAY k8644 enhances anterior pituitary secretion in rat and monkey.

A calcium channel agonist BAY k8644 was applied to anterior pituitary (AP) cells in vitro. BAY k8644 (0.1-10 microM) stimulated prolactin and growth hormone (GH) release from monolayer AP cultures; the calcium channel antagonist D-600 (1-10 microM) completely blocked this effect. By utilizing a perifusion system, we observed an immediate and sustained amplification of prolactin (2.9-fold), growth hormone (2.3-fold), and luteinizing hormone (LH, 1.6-fold) release during the 1-h application of BAY k8644 (3 microM). A hypophysiotrophic peptide pulse 4 h after the BAY k8644 was removed confirmed that the cells remained responsive to their natural secretagogues. In another perifusion study 10-3,000 nM BAY k8644 produced a graded increase in prolactin release that was maintained over the 30-min exposure period. Finally, individual primate mammotrophs and somatotrophs showed a marked enlargement of hemolytic plaque area, an index of hormone release, 1 h after BAY k8644 (1 microM). We conclude that this synthetic dihydropyridine enhances the rate of prolactin, GH, and LH release from AP cells of two species. Because this is the first synthetic calcium channel agonist, structure-function studies characterizing calcium channel activation and exocytosis are now feasible.

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

PubMed1991

Effects of calcium channel agonists (BAY K 8644, CGP28392 and YC-170) on 45Ca uptake by rat uterine segments.

The characteristics of the stimulating effects of the calcium channel agonists BAY K 8644, CGP28392 and YC-170 on 45Ca uptake by rat uterine segments were investigated. BAY K 8644, CGP28392 and YC-170 caused about 150, 100 and 150% increase, respectively in the 45Ca uptake induced by 20 mM KCl. The ED50 values of BAY K 8644, CGP28392 and YC-170 were 1.8 X 10(-9), 2.5 X 10(-8) and 9.8 X 10(-9) M, respectively. These agonists had little effect on the 45Ca uptake induced by 10(-6) M acetylcholine. They also did not affect the basal 45Ca uptake. Their enhancing effects were blocked by the Ca channel antagonist nitrendipine. We conclude that rat uterine segments have voltage-sensitive Ca channels that are stimulated by Ca channel agonists (BAY K 8644, CGP28392 and YC-170) under depolarizing conditions and that the characteristics of the stimulating effects of CGP28392 and YC-170 on 45Ca uptake by rat uterine segments are qualitatively the same as those of BAY K 8644.

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

PubMed1991

Effects of calcium channel agonist and antagonists on calcium-dependent events in CA1 hippocampal neurons.

The effects of a variety of calcium channel modulators on different calcium-dependent events in CA1 pyramidal hippocampal neurons were analysed using intracellular recordings in an in vitro slice preparation. The following substances were tested: the dihydropyridine calcium agonist BAY K 8644, the dihydropyridine calcium antagonist nimodipine, the phenylalkylamine verapamil and the snail toxin omega-conotoxin GVIA (omega-CgTx). BAY K 8644 increased the repolarization time of the after hyperpolarization (AHP) following a spike burst. This effect was antagonized by nimodipine. BAY K 8644 also prolonged the calcium spike and, in some cases, increased the size of the synaptic events resulting from activation of the Schaffer collateral/commissural system. Nimodipine decreased the size of the AHP in some neurons but had no consistent effect on synaptic events. Verapamil at low concentrations (1-10 microM) had no significant effects on the calcium-dependent events in the hippocampus. Increasing the concentration (up to 100 microM) led to a progressive suppression of the AHP and of the slow inhibitory postsynaptic potential (IPSP), probably via an action on potassium conductances. In addition, the baclofen-induced hyperpolarization was blocked by verapamil. Interestingly, at this higher concentration, verapamil could suppress the AHP without depressing the calcium spike. omega-CgTx selectively blocked the synaptic events (especially the IPSPs) but had no effect on non-synaptic events. This last compound exhibits a high degree of selectivity, acting on N-type calcium channels which are involved in neurotransmitter release. Our results provide evidence that different classes of agents which act on calcium channels can be used to discriminate between different calcium-dependent responses in CA1 hippocampal neurons.

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

PubMed1987

Inhibitory effects of calcium channel agonists on renin release from rat kidney cortical slices.

Inhibitory effects of calcium channel agonists such as Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate] and CGP 28392 [ethyl-4-(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl- 5-oxofuro-(3,4-b)-pyridine-3-carboxylate] on renin release were investigated, using rat kidney cortical slices. Bay K 8644 or CGP 28392 alone had no effect on renin release from the slices, whereas both compounds produced a concentration-dependent inhibition of the release in the presence of 15 mM potassium. The Bay K 8644-induced inhibitory action was more effective and potent than that seen with CGP 28392. Bay K 8644 caused a leftward shift of the dose-response curve of the potassium-induced decrease in renin release. In contrast, the dose-response relationships of the release to norepinephrine and methoxamine were not affected by Bay K 8644. The combination of the maximum effective doses of calcium channel agonists and norepinephrine exerted an apparent additive effect on the release of renin. The inhibitory effects of Bay K 8644 and CGP 28392 were attenuated in the presence of decreased extracellular calcium concentrations. Nifedipine and verapamil elicited a blocking action on the inhibition of renin release by Bay K 8644 or CGP 28392, in a concentration-dependent manner. Calmodulin antagonists, such as trifluoperazine and calmidazolium suppressed significantly the decreasing effect of Bay K 8644 or CGP 28392 on renin release from the slices.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1986

Selective enhancement of angiotensin II- and potassium-stimulated aldosterone secretion by the calcium channel agonist BAY K 8644.

Recent studies with dihydropyridine calcium channel antagonists have indicated that voltage-sensitive calcium channels (VSCC) play a major role in the control of aldosterone secretion. The modulation of VSCC by physiological regulators of zona glomerulosa function was further evaluated by analysis of the actions of the dihydropyridine calcium channel agonist BAY K 8644 (BK 8644) on basal and stimulated aldosterone production in isolated rat glomerulosa cells. In the presence of normal K+ concentrations (3.5-4.5 mM), only high concentrations of BK 8644 (greater than or equal to 100 nM) stimulated aldosterone secretion. However, addition of 10 nM BK 8644 markedly enhanced steroid production (70% over control) in cells stimulated by incubation in 7.5 mM K+ or 0.1 nM angiotensin II (AII). Greater enhancement was achieved with 1 microM BK 8644, with aldosterone secretion 150% and 300% above control levels for K+ and AII, respectively. In AII-stimulated cells, 30 nM BK 8644 enhanced aldosterone secretion at all peptide concentrations studied, including a 70% increase in the maximum steroid response, with no change in sensitivity to AII. In K+-stimulated cells, the effects of BK 8644 were dependent on the medium concentration of K+. At submaximally stimulating K+ concentrations (less than 9 mM), 30 nM BK 8644 increased the sensitivity of glomerulosa cells to K+ with no change in the maximal aldosterone response. However, at supramaximally stimulating concentrations of K+ (greater than 10 mM), BK 8644 reduced aldosterone production by 50%. In contrast to the effects of BK 8644 on cells stimulated with K+ or AII, the channel agonist had no effect on the action of ACTH. The ability of BK 8644 to enhance the maximum aldosterone response to AII suggests that AII, unlike K+, does not fully activate the Ca2+ influx pathway that leads to aldosterone secretion. Since BK 8644 is believed to facilitate Ca2+ influx primarily through previously activated channels, these results suggest that VSCC in the rat glomerulosa cell are partially operative under basal conditions, and that the same types of channels are further activated by AII and K+.

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

PubMed1988

Dopamine inhibits prolactin secretion stimulated by the calcium channel agonist Bay-K-8644 through a pertussis toxin-sensitive G protein in anterior pituitary cells.

In primary culture of anterior pituitary cells, BAY-K-8644, a calcium channel agonist, stimulated PRL secretion by 83% with EC50 of 18 nM. This effect was blocked by nifedipine, a calcium channel antagonist. The stimulations of PRL secretion induced by potassium (50 mM) and BAY-K-8644 were additive. Dopamine inhibited basal as well as BAY-K-8644-stimulated PRL secretion by 64% and 75%, respectively, and with respective EC50 values of 4.5 and 0.6 nM. In the presence of 50 mM K+, dopamine only partially blocks the dose-dependent stimulation of PRL secretion induced by the calcium channel agonist. The inhibitory dopamine effect was blocked by (+)butaclamol, a specific dopamine receptor antagonist. The dopamine response was also blocked by 1-sulpiride, a specific dopamine D2 receptor antagonist, and mimicked by RU 24926, a specific dopamine D2 receptor agonist, suggesting that the dopamine effect on BAY-K-8644-stimulated PRL secretion was mediated through a D2 dopamine receptor. Although unknown, the mechanism by which dopamine inhibited the BAY-K-8644-stimulated PRL secretion involves a GTP binding protein sensitive to Bordetella pertussis toxin. In fact, the dopamine inhibition of PRL secretion induced by the calcium channel agonist was blocked by the pretreatment of cells with the toxin. These results suggest that dopamine D2 receptors in lactotroph cells modulate calcium influx through a GTP binding protein.

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

PubMed1988

Modulation of anaphylactic histamine release by calcium channel agonists and antagonists.

Calcium antagonists have been reported to exert protective effects in hypersensitivity reactions in man and animals. However, their effect on anaphylactic histamine release is highly variable and controversial. In the present paper we evaluate the effect of calcium entry blockers and BAY K 8644 on the response to specific antigen in isolated hearts taken from actively sensitized guinea-pigs and from isolated rat and guinea-pig mast cells, actively or passively sensitized. Verapamil, diltiazem, nifedipine and prenylamine dose-dependently decreased anaphylactic histamine release in isolated actively sensitized guinea-pig mast cells. BAY K 8644 was found to be ineffective. In isolated, passively sensitized rat mast cells, verapamil showed a highly significant inhibitory effect, while prenylamine (10(-4) M) was able to evoke a histamine releasing effect. In cardiac anaphylaxis verapamil, diltiazem, prenylamine, but not nifedipine, were active in reducing the release of histamine without modifying the antigen-induced arrhythmias and positive chronotropic and inotropic effects.

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

PubMed1989

Regulation of beta-adrenergic receptors and calcium channel agonist binding sites in cultured human embryonal smooth muscle cells.

Recent electrophysiological studies with cell membrane patches of cardiac myocytes and an electrically excitable cell line derived from rat pituitary tumor suggested that voltage activated calcium channels must be phosphorylated to respond to membrane depolarization (Armstrong and Eckert 1986; Trautwein and Kameyama 1986). In view of the "phosphorylation hypothesis" we investigated the adenylate-cyclase activity, the characteristics of beta-adrenergic and calcium channel agonist binding sites in control and desensitized (exposure to isoproterenol) human embryonal cells (HEC), and in fragmented membrane preparations of canine coronary smooth muscle. Our results suggest that down-regulation of the membrane-bound beta-adrenergic receptors, induced by isoproterenol in human embryonal cells and also in adult canine vascular tissue, results in physical translocation of beta-adrenergic binding sites into the light membrane fraction. This phenomenon is accompanied with an increased intracellular concentration of cAMP in and an increased binding of the calcium channel agonist (3H) BAYK 8644 to both HEC and canine smooth muscle membrane preparations. It could be concluded that phosphorylation of beta-adrenergic receptors regulates not only the beta subcellular distribution of the beta receptors but also the availability of calcium channel agonist binding sites in the cellular membrane.

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