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Biomedical subjects

E Anselmi

Publications and source records attributed to E Anselmi.

At least 19 recordsLinked to original sources
PubMed2005

Oncologic emergencies secondary to advanced colorectal cancer successfully treated with oxaliplatin/5-fluorouracil/leucovorin: report of three cases.

Metastatic/advanced colorectal cancer is considered a resistant disease and oncologic emergencies secondary to advanced disease may be regarded with a nihilistic attitude. The objective of this report is to emphasize the efficacy of the oxaliplatin/5-fluorouracil/leucovorin regimen (FOLFOX-4) in three patients presenting oncologic emergencies secondary to advanced colon cancer. The first case was a 40-year-old man with severe respiratory insufficiency due to massive carcinomatous lymphangitis; subsequently a cecal adenocarcinoma was diagnosed. The patient's conditions became life-threatening and he was admitted to the intensive care unit. The second case was a 41-year-old woman presenting with fever, abdominal mass and pain. Ultrasound and CT-scan revealed two hepatic masses (13 x 15 and 15 x 20 cm), diagnosed as liver metastases from colon cancer. The patient's condition deteriorated with intestinal obstruction secondary to the large left liver mass. The third case was a 58-year-old woman presenting with hepatic mass, fever and weight loss. Ultrasound and CT-scan showed a liver lesion occupying the right lobe (12 x 14 cm). Ultrasonically-guided biopsy and colonoscopy showed liver metastases from cecal cancer. A 5-fluorouracil/leucovorin regimen failed to improve her clinical condition and she had disease progression, inferior vena cava neoplastic thrombosis and right hydronephrosis. All three patients rapidly improved after a few cycles of oxaliplatin-containing chemotherapy. These cases demonstrate that even patients with advanced colorectal cancer presenting with oncologic emergencies and life-threatening conditions can be successfully treated with the FOLFOX-4 regimen.

Acute Disease↗
PubMed2004

Acute and chronic captopril, but not prazosin or nifedipine, normalize alterations in adrenergic intracellular Ca2+ handling observed in the mesenteric arterial tree of spontaneously hypertensive rats.

The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg(-1) per day), nifedipine (50 mg kg(-1) per day), or captopril (50 mg kg(-1) per day) on Ca2+ mobilization due to alpha1-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca2+ is not affected by hypertension or by the antihypertensive treatment. The extracellular Ca2+-independent contractile responses increased with age in iliac, tail, and small mesenteric arteries (SMA) and were further increased in SHR in SMA from both young and adult animals and in the main mesenteric artery of adult SHR. In main mesenteric artery, this increased contraction in SHR was associated with a higher increase in cytosolic [Ca2+] mobilized by noradrenaline without changes in the total stored Ca2+. Acute or chronic treatment with captopril abolished the differences observed between WKY and SHR in the noradrenaline-induced contraction in mesenteric arteries loaded in Ca2+-free medium. In contrast, animals acutely treated with prazosin or chronically treated with either prazosin or nifedipine exhibit the same differences in Ca2+ handling than untreated rats. In conclusion, these differences are not a consequence of increased blood pressure but precede it and can only be normalized by inhibition of the rennin-angiotensin system.

Adrenergic alpha-Antagonists↗
PubMed2001

Changes in the expression of tachykinin receptors in the rat uterus during the course of pregnancy.

In the mammalian female reproductive tract, tachykinin neuropeptides, such as substance P (SP), are localized to a population of sensory fibers and their precise physiological role is still unknown. The aim of the present study was to characterize the population of tachykinin receptors in the pregnant rat uterus and to assess their regulation during the course of pregnancy and after delivery. The expression of the tachykinin NK(1) receptor (NK(1)R), the tachykinin NK(2) receptor (NK(2)R), and the tachykinin NK(3) receptor (NK(3)R) in uteri from rats at different stages of pregnancy and on Day 1 postpartum was investigated by using a semiquantitative reverse transcription-polymerase chain reaction. The contractile effect of tachykinin receptor agonists acting selectively on the NK(1)R, the NK(2)R, or the NK(3)R was investigated by conventional organ bath techniques. Serum levels of estrogen and progesterone were measured by RIA. Our data show that the expression and function of NK(1)R and NK(3)R varied along the course of pregnancy and at postpartum. Uterine NK(2)R mRNA levels remain stable during the course of pregnancy and at Day 1 postpartum; and the contractions elicited by activating selectively the NK(2) receptor in the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM) were similar in early, mid, or late pregnancy. These results show that the expression and function of tachykinin receptors within the uterus vary with reproductive state and length of gestation, supporting a role for tachykinins in pregnancy and/or parturition in the rat.

Animals↗
PubMed2000

Mechanism of vascular relaxation by thaligrisine: functional and binding assays.

In the present study we examine the mechanism by which thaligrisine, a bisbenzyltetrahydroisoquinoline alkaloid, inhibits the contractile response of vascular smooth muscle. The work includes functional studies on rat isolated aorta and tail artery precontracted with noradrenaline or KCl. In other experiments rat aorta was precontracted by caffeine in the presence or absence of extracellular Ca2+. In order to assess whether thaligrisine interacts directly with calcium channel binding sites or with alpha-adrenoceptors we examined the effect of the alkaloid on [3H]-(+)-cis diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The functional studies showed that the alkaloid inhibited in a concentration-dependent manner the contractile response induced by depolarization in rat aorta (IC50 = 8.9+/-2.9 microM, n=5) and in tail artery (IC50 = 3.04+/-0.3 microM, n=6) or noradrenaline induced contraction in rat aorta (IC50 = 23.0+/-0.39 microM, n=9) and in tail artery (IC50 = 3.8+/-0.9 microM, n=7). In rat aorta, thaligrisine concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 = 13.3 microM, n=18). The alkaloid also relaxed the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (IC50 = 7.7 microM, n=4). The radioligand receptor-binding study showed that thaligrisine has higher affinity for [3H]-prazosin than for [3H]-(+)-cis-diltiazem binding sites, with Ki values of 0.048+/-0.007 microM and 1.5+/-1.1 microM respectively. [3H]-nitrendipine binding was not affected by thaligrisine. The present work provides evidence that thaligrisine shows higher affinity for [3H]-prazosin binding site than [3H]-(+)-cis-diltiazem binding sites, in contrast with tetrandrine and isotetrandrine that present similar affinity for both receptors. In functional studies thaligrisine, acted as an alpha1-adrenoceptor antagonist and as a Ca2+ channel blocker, relaxing noradrenaline or KCl-induced contractions in vascular smooth muscle. This compound specifically inhibits the refilling of internal Ca2+-stores sensitive to noradrenaline, by blocking Ca2+-entry through voltage-dependent Ca2+-channels.

Adrenergic alpha-Agonists↗
PubMed1998

Characterization of tachykinin receptors in the uterus of the oestrogen-primed rat.

1 The aim of our study was to characterize the tachykinin receptor population in the oestrogen-primed rat uterus. For this purpose, we investigated the receptor type(s) responsible for tachykinin-induced contraction of longitudinally-arranged smooth muscle layer. The effects of substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and several of their analogues with well-defined selectivities for tachykinin NK1, NK2 and NK3 receptors were studied and their inhibition by the selective nonpeptide tachykinin receptor antagonists (S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3-yl]ethyl)-4-phenyl- -azoniabicyclo[2.2.2]octane chloride (SR 140333, NK1-selective), (S)-N-methyl-N[4-(4acetylamino-4-phenylpiperidino)-2-(3,4-dichloro phenyl)butyl]benzamide (SR 48968, NK2-selective) and (R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N- methyla-cetamide (SR 142801, NK3-selective) was evaluated. Additionally, expression of tachykinin receptor mRNA was examined by using the reverse transcription-polymerase chain reaction (RT-PCR). 2 SP, NKA, [Nle10]-NKA(4-10), the analogue with selectivity at the tachykinin NK2 receptor type, and NKB elicited concentration-dependent contractions of the rat uterus. The pD2 values were 5.95+/-0.19; 6.73+/-0.21; 7.53+/-0.12 and 5.76+/-0.21, respectively. The selective agonist for the tachykinin NK1 receptor [Sar9Met(O2)11]-SP produced a small phasic response in the nanomolar concentration range. The selective tachykinin NK3 receptor agonist [MePhe7]-NKB failed to induce any significant contraction. 3 In the presence of the neutral endopeptidase inhibitor phosphoramidon (1 microM), the log concentration-response curves to exogenous tachykinins and their analogues were shifted significantly leftwards. The pD2 values were 6.12+/-0.10, 8.04+/-0.07, 7.89+/-0.03 and 6.59+/-0.07 for SP, NKA, [Nle10]-NKA(4-10) and NKB, respectively. In the presence of phosphoramidon (1 microM), [Sar9Met(O2)11]-SP (1 nM - 0.3 microM) induced concentration-dependent contractions of increasing amplitude when only one concentration of drug was applied to each uterine strip and the pD2 value was 7.61+/-0.89. [MePhe7]-NKB induced small, inconsistent contractions and, therefore, a pD2 value could not be calculated. 4 In experiments performed in the presence of phosphoramidon (1 microM), SR 48968 (3 nM - 0.1 microM) caused parallel and rightward shifts in the log concentration-response curves of NKA. The calculated pKB value was 9.16+/-0.08 and the slope of the Schild regression was 1.28+/-0.24. SR 48968 (0.1 microM) also antagonized responses to SP with an apparent pKB value of 7.63+/-0.13. SR 48968 (0.1 microM) inhibited contractions elicited by NKB (1 nM - 3 microM) and [Nle10]-NKA(4-10) (0.1 nM - 3 microM) but had no effect on the response evoked by [Sar9Met(O2)11]-SP (0.1 microM). 5 SR 140333 (0.1 microM) inhibited responses to SP with an apparent pKB value of 7.19+/-0.22. This compound did not significantly affect responses to NKA, [Nle10]-NKA(4-10) and NKB, but suppressed [Sar9Met(O2)11]-SP (0.1 microM)-induced contraction. SR 142801 (0.1 microM) had no effect on responses to natural tachykinins or their analogues. 6 Total RNA was extracted from some of the uteri used in functional studies. RT-PCR assays revealed single bands corresponding to the expected product sizes encoding cDNA for tachykinin NK1 (587 base pairs) and NK2 receptors (491 base pairs) (n=6 different animals). A very low abundance transcript corresponding to the 325 base pairs product expected for the tachykinin NK3 receptor was detected. 7 The present data show that functionally active tachykinin NK1 and NK2 receptors are expressed in the oestrogen-primed rat uterus. The NK2 receptor type seems to be the most important one involved in the contractile responses elicited by tachykinins. NK3 receptors are present in trace amounts and seem not to be involved in tachykinin-induced contractions.

Animals↗
PubMed1998

Alpha-adrenoceptor interaction of tetrandrine and isotetrandrine in the rat: functional and binding assays.

The action of 1S,1'S-tetrandrine, a bisbenzyltetrahydroisoquinoline alkaloid, on alpha1-adrenoceptors has been compared with that of its isomer 1R,1'S-isotetrandrine. The work includes binding assays to analyse the affinity of these products for the [3H]prazosin binding site of rat cerebral cortical membranes and functional studies on rat isolated aorta to examine the effects of both alkaloids on intracellular calcium processes related or not to alpha-adrenoceptor activation. A radioligand receptor-binding study showed that both compounds interacted with the alpha1-adrenoceptors displacing [3H]prazosin from the specific binding site. The Ki values (inhibition constants) were 0.69+/-0.12 and 1.6+/-0.4 microM for tetrandrine and isotetrandrine, respectively. The functional studies showed that both alkaloids concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 values, i.e. the concentrations needed to induce 50% inhibition, were 252.8 and 174.9 microM for tetrandrine and isotetrandrine, respectively), the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (increase in resting tone; IC50 values 11.6 and 19.6 microM for tetrandrine and isotetrandrine, respectively) and the refilling of intracellular Ca2+ stores sensitive to noradrenaline (IC50 values 7.4 and 14.9 microM for tetrandrine and isotetrandrine, respectively). The results show that tetrandrine and isotetrandrine interact with alpha1-adrenoceptors by displacing the [3H]prazosin binding site and that both compounds inhibit mainly the Ca2+-dependent process and have less action on alpha1-adrenoceptors. Tetrandrine is more potent than isotetrandrine.

Alkaloids↗
PubMed1998

The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline alkaloids on rat aorta.

The action of four benzylisoquinoline alkaloids (two aporphines-glaucine and apomorphine, a benzylisoquinoline-papaverine and a bisbenzyltetrahydroisoquinoline-antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl. The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the alpha1-adrenoceptor and nifedipine seems to have a more potent effect on KCl-induced contraction than on that induced by 5-HT or noradrenaline. The contraction evoked by 5-HT (10 microM) was inhibited in a concentration-dependent manner by all the alkaloids. The order of potency was: papaverine = glaucine > apomorphine > antioquine. Papaverine had a non-specific relaxant action on 5-HT-, noradrenaline- and KCl-induced contraction, antioquine had a weak relaxant action on the agonist assays, and glaucine and apomorphine inhibited noradrenaline- and 5-HT-induced contraction more potently than they inhibited the K+-depolarized response. These results indicate that the aporphines assayed, S-glaucine and R-aporphine, had selective action against agonist (noradrenaline or 5-HT)-induced contraction rather than against KCl-depolarization of rat aorta. In contrast papaverine, a benzylisoquinoline alkaloid, relaxes all agents used non-selectively as could be expected from the lack of specificity that characterizes this alkaloid.

Adrenergic alpha-Antagonists↗
PubMed1997

Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen-primed rat uterus.

We investigated the effect of Mn2+ on the mechanical responses evoked by high K+ (60 mM) or low Na+ (25 mM) solutions, oxytocin and neurokinin A in the oestrogen-primed rat uterus. In a Ca2+-free, Mn2+ (0.54 mM)-containing solution, high K+ or low Na+ solutions produced contractions of smaller amplitude than those observed in a normal Ca2+ (0.54 mM) solution, which were abolished by nifedipine (1 microM). Oxytocin (1 microM) and neurokinin A (1 microM, in the presence of phosphoramidon 1 microM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca2+ (0.54 mM)-containing solution. In strips loaded with Ca2+ (2.16 mM) for 10 min and then exposed to a Ca2+- and Mn2+-free, EGTA (3 mM)-containing medium for 4 min, both oxytocin and neurokinin A induced transient contraction followed by a small sustained response. The transient component of the response was abolished by cyclopiazonic acid (10 microM). When preparations were loaded with Mn2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In Ca2+-containing solution, Mn2+ (0.01-10 mM) inhibited in a concentration-dependent manner the rhythmic contractions developed either spontaneously or by electrical stimulation as well as high K+- and neurokinin A-induced contractions. Mn2+ also abolished the rhythmic, but not the tonic component of the response to oxytocin, and the preparation remained maximally contracted. These data suggest that in the oestrogen-primed rat uterus, Mn2+ acts as an antagonist of Ca2+ influx through L-type voltage-operated Ca2+ channels. In addition, Mn2+ enters the cell mainly through nifedipine-insensitive receptor-operated channels and, to a lesser degree, through L-type Ca2+ channels to produce contraction by directly activating the contractile machinery.

Animals↗
PubMed1997

Regulation by oestrogens of tachykinin NK3 receptor expression in the rat uterus.

The expression of the tachykinin NK3 receptor and its regulation by ovarian steroids were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in uteri from ovariectomized rats. A single transcript corresponding to the 325-bp product expected for the tachykinin NK3 receptor was detected in uteri from olive oil-treated (control) ovariectomized rats. The level of tachykinin NK3 receptor mRNA in progesterone-treated animals was similar to that observed in uteri from control ones. Tachykinin NK3 receptor mRNA levels were significantly smaller in uteri from oestrogen-treated ovariectomized rats, with approximately a 32-fold decrease. These findings suggest that oestrogen, but not progesterone, regulates the expression of tachykinin NK3 receptors in the rat uterus.

Animals↗
PubMed1996

The sources of Ca2+ for muscarinic receptor-induced contraction in the rat ileum.

The contractile responses obtained by activation of different muscarinic receptor subtypes in the longitudinal muscle of the rat ileum and especially the responses of this muscle to acetylcholine in a Ca(2+)-free medium have been investigated. In Ca(2+)-containing solution, acetylcholine elicited similar concentration-dependent contractile responses in the duodenum, jejunum and ileum strips of the rat intestine. The response to a maximal concentration of the agonist (1 microM) consisted of a rapid phasic response followed by a slower tonic one. Nifedipine completely relaxes or inhibits the sustained response and only partially diminishes the phasic one, which suggests that the phasic contraction depends on the release of internal Ca2+ entry from the extracellular space through voltage-dependent Ca2+ channels, but that the tonic contraction only depends on the influx of the external ion. In Ca(2+)-free medium, acetylcholine (1 microM) induced phasic contractions that depend on the release of this ion from internal stores. Participation of different subtypes of receptors (M1, M2 and M3) in these responses depends on the inhibitory action shown by methoctramine, 4-DAMP and atropine but not by pirenzepine in two different experimental models.

Acetylcholine↗
PubMed1994

Influence of the absolute configuration on the vascular effects of tetrandrine and isotetrandrine in rat aorta.

The relaxant action of (1S, 1'S) tetrandrine and its isomer (1R, 1'S) isotetrandrine were examined in rat aortic strips, in presence or absence of extracellular calcium. Both alkaloids relax, concentration dependently, the contractile response elicited by depolarizing solution (KCl 80 mM) or noradrenaline (1 microM). Tetrandrine, however, showed a selectivity of action towards the KCl-induced contraction while isotetrandrine did not. In Ca(2+)-free solution, both alkaloids inhibited the contraction induced by noradrenaline, but they did not affect the transient contraction due to caffeine then this effect is not attributable to direct inhibition of the smooth muscle contractile elements. The refilling of intracellular calcium stores sensitive to noradrenaline or caffeine was significantly inhibited by both alkaloids.

Alkaloids↗
PubMed1993

Investigations of the dual contractile/relaxant properties showed by antioquine in rat aorta.

1. In the present study we assessed the activity of antioquine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from Pseudoxandra sclerocarpa, by examining its effects on the contractile activity of rat isolated aorta, specific binding of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin to cerebral cortical membranes and the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta. 2. Contractions in rat aorta induced by high concentrations of KCl (80 mM) and noradrenaline (1 microM) were inhibited by antioquine in a concentration-dependent manner (0.1 microM- 300 microM). The alkaloid appeared more potent against KCl-induced contractions. This inhibitory effect was observed at both 37 degrees C and 25 degrees C. 3. Paradoxically, at the highest concentration tested (300 microM) antioquine induced a contractile response of similar magnitude in the presence and absence of extracellular calcium, at 37 degrees C. This activity was greatly attenuated at 25 degrees C. Antioquine-induced contractions were not inhibited by prazosin (0.1 microM), nifedipine (1 microM) or diltiazem (100 microM). On the contrary, prazosin and nifedipine slightly increased the contractions in the presence of extracellular calcium. Papaverine (100 microM) partially inhibited the contractile response to antioquine both in the presence and absence of extracellular calcium. 4. At 25 degrees C, in Ca(2+)-free solution, antioquine (300 microM) did not modify the contractile response (phasic and tonic) evoked by noradrenaline, but increased the phasic contraction induced by caffeine. At 37 degrees C, the contraction elicited by antioquine made it impossible to observe the noradrenaline-induced one. 5. Antioquine showed affinity for the [3H]-prazosin binding site and for the [3H]-(+)-cis-diltiazembinding site of the Ca2+-channel receptor complex, but had no effect at the dihydropyridine binding site in rat cerebral cortex.6. Antioquine weakly inhibited some PDE forms isolated from bovine aorta: a CaM-PDE (PDE I)which preferentially hydrolyzes cyclic GMP and is activated by calmodulin, and a rolipram-sensitive cyclic AMP-PDE (PDE IV) which hydrolyzed cyclic AMP. Antioquine did not exert any inhibitory effect on the other forms of PDE, a cyclic GMP selective form (PDE V) and a low Km cyclic AMP-PDEthat is inhibited by cyclic GMP (CGI-PDE, PDE III).7. The present work provides evidence that antioquine has properties both as a calcium entry blocker(possibly through the benzothiazepine recognition site in the calcium channel) and as a contractile agent.Its mechanism of action as a contractile agent is not related to Ca2+-entry and is hypothetically similar to that of calyculin-A or okadaic acid. The possible involvement of a-adrenoceptors in this paradoxical effect cannot be excluded. The rigidity of the molecule provides an interesting model for analyzing this contractile mechanism and the intracellular processes involved.

Alkaloids↗
PubMed1993

Comparative study of the rat uterine smooth muscle relaxant activity of three bisbenzyltetrahydroisoquinolines with tetrandrine.

The relaxant activity of three bisbenzyltetrahydroisoquinolines--obaberine, popisonine and lindoldhamine--was examined in rat isolated uterus and their inhibitory potencies were compared with that of tetrandrine. All alkaloids tested relaxed KCl-depolarized rat uterus and totally or partially inhibited oxytocin-induced rhythmic contractions. The degree of methylation of the free phenolic hydroxy groups and the loss of one diarylether bridge influence the potency of relaxant action of these alkaloids. Only alkaloids with absolute configuration 1R,1'S or 1R1'R acted intracellularly, promoting relaxation of contractile responses induced by oxytocin or vanadate in a Ca(2+)-free medium.

Alkaloids↗
PubMed1992

Multiple actions of glaucine on cyclic nucleotide phosphodiesterases, alpha 1-adrenoceptor and benzothiazepine binding site at the calcium channel.

1. In the present study, the properties of glaucine (an aporphine structurally related to papaverine) were compared with those of papaverine, diltiazem, nifedipine and prazosin. The work includes functional studies on rat isolated aorta contracted with noradrenaline, caffeine or KCl, and a determination of the affinity of glaucine at calcium channel binding sites of alpha-adrenoceptors, by use of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The effects of glaucine on the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta were also determined. 2. Contraction evoked by noradrenaline (1 microM) or depolarizing solution (60 mM KCl) were inhibited in a concentration-dependent manner by all the compounds tested. As expected, prazosin showed a greater selectivity of action on NA-induced contraction, whereas nifedipine and diltiazem appeared more potent on KCl-induced contraction. Glaucine had a greater potency on the contraction elicited by noradrenaline whereas papaverine acted non specifically. 3. In Ca(2+)-free solution, prazosin (0.1 microM) and glaucine (0.1 mM) inhibited the contraction evoked by NA; diltiazem (0.1 mM) diminished this contraction whereas nifedipine (1 microM) had no effect. Preincubation of tissues with glaucine, diltiazem, nifedipine and prazosin did not modify the contractile response induced by caffeine. In contrast, papaverine (0.1 mM) significantly inhibited the contractions evoked by NA or caffeine in Ca(2+)-free medium. 4. Glaucine and papaverine show affinity at the [3H]-prazosin binding site and at the benzothiazepine binding site of the Ca(2+)-channel receptor complex, but have no effect at the dihydropyridine binding site in rat cerebral cortex. Glaucine exerts some selectivity as an inhibitor of [3H]-prazosin binding as opposed to [3H]-(+ )-cis-diltiazem binding while papaverine appears to have approximately equal affinity in this respect.5. This study confirms the presence of four phosphodiesterase (PDE) activities in bovine aorta: a calmodulin-activated PDE (CaM-PDE type I) which hydrolyzed preferentially guanosine 3':5'-cyclic monophosphate (cyclic GMP); a cyclic GMP selective form (cGMP-PDE type V); and two low Km adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDEs that are insensitive to the stimulatory effect of CaM, one of which was inhibited by cyclic GMP (CGI-PDE, type III) and the other by rolipram (cAMP-PDE, type IV). Glaucine selectively inhibits one of the two forms of Ca2+-independent low Km cAMP-PDE, the type IV. In contrast, papaverine exerts a non-selective inhibitory effect upon all PDE forms.6. The present work provides evidence that glaucine, a benzyltetrahydroisoquinoline alkaloid, has interesting properties as an alpha l-adrenoceptor antagonist, calcium entry blocker (through the benzothiazepine recognition site in the calcium channel) and as a selective inhibitor of the rolipram-sensitive cAMP-PDE, type IV PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Selective inhibition of calcium entry induced by benzylisoquinolines in rat smooth muscle.

The mechanism of relaxant activity of six benzylisoquinolines was examined in order to determine the minimal structural requirements that enable these compounds to have either a non-specific action like papaverine or an inhibitory activity on calcium entry via potential-operated channels. All the alkaloids tested totally or partially relaxed KCl-depolarized rat uterus and inhibited oxytocin-induced rhythmic contractions. Only glaucine and laudanosine inhibited K(+)-induced uterine contractions more than oxytocin-induced uterine contractions. In Ca(+)-free medium, sustained contractions induced by oxytocin or vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine indicating no inhibitory effect on intracellular calcium release. Those alkaloids containing an unsaturated heterocyclic ring (papaverine, papaverinol, papaveraldine, N-methylpapaverine and dehydropapaverine) exhibited a more specific activity than those with a tetrahydroisoquinoline ring.

Alkaloids↗
PubMed1992

Tetrandrine and isotetrandrine, two bisbenzyltetrahydroisoquinoline alkaloids from Menispermaceae, with rat uterine smooth muscle relaxant activity.

The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S,1'S tetrandrine and its isomer 1R,1'S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca(2+)-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversible manner whilst only isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant activity as a calcium entry blocker.

Acetylcholine↗
PubMed1989

A study of beta-adrenoceptors in rat lung parenchymal strip.

The aim of the present study was to characterize the beta-adrenoceptor population in rat lung strip. For this purpose, Schild plots were obtained for the beta-adrenoceptor antagonists atenolol (beta 1-selective), butoxamine (beta 2-selective) and propranolol (non-selective), using three different agonists:isoprenaline (non-selective), salbutamol (beta 2-selective) and noradrenaline (beta 1-selective). The slopes of these Schild plots were close to the theoretical value of unity, and pA2 values determined with isoprenaline, salbutamol and noradrenaline as agonists were: for propranolol, 7.86 +/- 0.22, 7.72 +/- 0.15 and 7.89 +/- 0.23; for atenolol, 5.19 +/- 0.05, 5.33 +/- 0.07 and 5.47 +/- 0.22 and for butoxamine, 6.31 +/- 0.11, 6.34 +/- 0.03 and 5.99 +/- 0.23, respectively. These data suggest that pharmacological responses of rat isolated lung strip to beta-adrenoceptor agents are mediated by a homogeneous population of beta 2-adrenoceptors, although the presence of a minor population of beta 1-adrenoceptors undetected by the agonists used cannot be excluded.

Albuterol↗