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PubMed1991

Effects of papaverine on tension and 45Ca-uptake in isolated urinary bladder.

Papaverine is believed to relax smooth muscle by reducing transmembrane calcium transport and cyclic nucleotide phosphodiesterase activity. The present study characterizes the different relaxing effects of papaverine on isolated muscle strips of rat bladder dome. Compared to histamine, norepinephrine and serotonin, carbachol and high potassium induced the most prominent contractions in rat bladder strips. For this reason both agents were used as stimulants. High-potassium-induced muscle contractions were reduced by a lower concentration of papaverine than carbachol-induced muscle concentrations. Compared to verapamil, papaverine, especially in low concentrations, was less potent on both kinds of induced muscle contractions. These tension responses correspond to a difference in 45Ca uptake, suggesting a nonspecific blocking property of papaverine on transmembrane calcium channels. The beta-sympathomimetic effects of isoprenaline on carbachol-induced contractions were not enhanced by verapamil. In contrast, papaverine increased this tension response of isoprenaline on carbachol-induced contraction. From these results it is possible that part of the papaverine action seems to be related to an intracellular mechanism probably to cAMP.

Animals↗
PubMed1985

Inhibitory effect of papaverine on RNA and protein synthesis of vesicular stomatitis virus.

Papaverine, an inhibitor of cAMP phosphodiesterase, reduced yields of infectious vesicular stomatitis virus in HEp-2 cells approximately 100-fold if added to cultures at a concentration of 30 microM before and after virus infection. The extent of papaverine-induced suppression of viral growth was dependent on drug dose and treatment regimen. Cells progressively recovered their viral permissive state after removal of drug. The cyclic nucleotide, cGMP, nullified the inhibitory effect of papaverine if added to cells during drug treatment. Pulse labeling experiments with [35S]methionine showed that papaverine compromises production of all virus-specific proteins in infected cells without adversely affecting host cell protein synthesis. Treatment of cells with papaverine strongly inhibited the production of viral RNA and both cellular RNA and DNA. It was found that VSV causes an immediate but transient stimulation of DNA synthesis in HEp-2 cells which is prevented by papaverine treatment. This drug also selectively blocked primary transcription of VSV in vivo and to a lesser extent in vitro RNA polymerase activity of the virion-bound transcriptase. The finding that papaverine has a strong inhibitory effect on viral biosynthesis including early transcription suggests that VSV replication may depend on host factors that regulate intracellular levels of cyclic nucleotides such as cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Synergistic effect of hyperthermia, papaverine, and chemotherapy in murine neuroblastoma.

The effects of microwave induced hyperthermia, papaverine, and chemotherapy were evaluated in transplanted CI300 murine neuroblastoma. One hundred forty-five Ajax mice received axillary subcutaneous implants of CI300 round cell neuroblastoma (1.25 X 10(6) cells). Animals were divided into 8 treatment groups: Group 1 (n = 14) received no therapy (controls); Group 2 (n = 20) received radiofrequency microwave hyperthermia (2450 MHz at 40 milliwatts/cm2 for 4 min at 41.5 decrees C); Group 3 (n = 14) received papaverine (65 mg/kg for 3 days); Group 4 (n = 14) received a single intraperitoneal injection of cyclophosphamide (CPM) (50 mg/kg) and vincristine (VCR) (0.2 mg/kg); Group 5 (n = 22) received papaverine, cyclophosphamide, and vincristine as above; Group 6 (n = 20) received hyperthermia and papaverine; Group 7 (n = 18) received hyperthermia, cyclophosphamide, and vincristine; and Group 8 (n = 19) received hyperthermia, papaverine, cyclophosphamide, and vincristine. Therapy was instituted at 21 days after implant (tumor size 1 cm2), continuing for 2 weekly cycles. Animals were assessed for tumor regression, survival and relapse free rate at 1 and 4 wk. Tumor regression was seen only in animals receiving chemotherapy. Initial response rate (1 week) was 50% (group 4), 55% (group 5), 89% in (group 7), and 100% in mice receiving chemotherapy, papaverine, and hyperthermia (group 8) (p less than 0.05 7 and 8 versus 4 and 5). At 4 wk however, tumor relapse was noted in 6 of 7 group 4 responders, 10 of 12 in group 5, 13 of 16 in group 7, but only 4 of 19 group 8 responders (p less than .001 group 8 versus 4, 5, 7). These data indicate a synergistic effect of papaverine, microwave induced hyperthermia and chemotherapy in murine neuroblastoma. These observations suggest such treatment may be useful in clinical instances of neuroblastoma, especially in nonresponders to conventional therapy.

Animals↗
PubMed1991

Sympathetic inhibition of papaverine induced erection.

We studied the effect of neurostimulation of the lumbar sympathetic trunks on papaverine-induced penile erection in dogs and monkeys. The mean of 124 cm. H2O intracavernous pressure after papaverine injection was reduced under sympathetic trunk stimulation to 40.6 cm. H2O within a mean of 39 sec. In addition the flow of the internal pudendal artery was reduced indicating a decrease of the inflow to the penis. After the sympathetic stimulation was terminated, the intracavernous pressure increased again to the same level as before. This pressure recovery time was delayed after several sympathetic stimulations from 134 sec. (5 min. after papaverine injection) to at least 362 sec. (45 minutes after papaverine injection). Stimulation of the inferior hypogastric plexus had no effect on the intracavernous pressure. The neurostimulation range (3-4V; 20 Hz) was most effective in reducing the papaverine action on penile smooth muscles. The effect of sympathetic trunk stimulation seems to antagonize the relaxing action of papaverine on the cavernous smooth muscles and the cavernous arterioles. Our results imply that high sympathetic tone in some patients with psychogenic impotence may explain their poor response to intracavernous injection of papaverine.

Animals↗
PubMed1990

Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum.

The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.

Calcium↗
PubMed1987

The erectile angle: objective criterion to evaluate the papaverine test in impotence.

Intracavernous papaverine injection may be the first diagnostic step in the assessment of the impotent patient. However, the appreciation of its effect must rely on the evaluation of penile rigidity. Since measurement of rigidity requires a sophisticated procedure that may not be available to the majority of practitioners, we attempted to find a simple and objective method to evaluate the results of this common test. We tested 50 patients complaining of impotence with intracavernous injection of 60 mg. papaverine. The length and circumference of the penis were measured before and after papaverine injection. The rigidity was determined by measuring the angle between the penis and the legs with the patient in the standing position. Afterwards, each patient underwent vascular (Doppler ultrasound and cavernometry) and neurological examinations. A total of 27 patients with no vascular abnormalities had an erectile angle of 96 degrees (range 90 to 130 degrees), while 23 patients had some vascular disorders (9 arterial lesions, 8 venous leakage and 6 combined lesions) and an erectile angle of 36 degrees (range 0 to 60 degrees). There was no significant difference between the groups in the increase of length and circumference of the penis after intracavernous injection of papaverine. The papaverine test can distinguish between patients with vascular and psychogenic problems. A negative papaverine test associated with a normal Doppler examination is characteristic of venous leakage. Measurement of the erectile angle after intracavernous injection of papaverine with the patient in the standing position is a simple, objective and reliable method to evaluate patients with vascular impotence.

Adult↗
PubMed2002

Papaverine induces apoptosis in vascular endothelial and smooth muscle cells.

Papaverine is a vasodilator commonly used in the treatment of vasospasmic diseases such as cerebral spasm associated with subarachnoid hemorrhage, and in the prevention of spasm of coronary artery bypass graft by intraluminal and/or extraluminal administration. In this study, we examined whether papaverine in the range of concentrations used clinically causes apoptosis of vascular endothelial and smooth muscle cells. Apoptotic cells were identified by morphological changes and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In porcine coronary endothelial cells (EC) and rat aortic smooth muscle cells (SMC), papaverine at the concentration of 10(-3) M induced membrane blebbing within 1 hour of incubation. Nuclear condensation and fragmentation were found after 24 hours of treatment. The number of apoptotic cells stained with the TUNEL method was significantly higher in the EC and the SMC after 24 hours of incubation with papaverine at the concentrations of 10(-4) and 10(-3) M than their respective controls. Acidified saline solution (pH 4.8, as control for 10(-3) M papaverine hydrochloride) did not cause apoptosis in these cells. These results showed that papaverine could damage endothelial and smooth muscle cells by inducing changes which are associated with events leading to apoptosis. Since integrity of endothelial cells is critical for normal vascular function, vascular administration of papaverine for clinical use, especially at high concentrations (> or = 10(-4) M), should be re-considered.

Animals↗
PubMed2004

Effect of intraurethral papaverine on penile erection in rats.

OBJECTIVES: The aim of this study is to investigate erectile response to intraurethral administration of papaverine in rats. MATERIAL AND METHODS: Male Sprague-Dawley rats were used in this study. Under urethane anesthesia, penis was exposed and intracavernous pressure (ICP) was recorded through a 23-gauge needle, which was inserted into right corpus cavernosum. Effects of intraurethral application of incremental doses of 0.2 ml papaverine gel (4-17.5 mg) on intracavernosal pressure were observed and compared with those of 0.4 mg papaverine applied into corpus cavernosum. Mean arterial blood pressure (MABP) and heart rate were also monitored. RESULTS: The mean basal ICP was 8.9 +/- 1.8 mm Hg. Intraurethral administration of papaverine did not increase ICP at any doses used in this study. After intracavernous injection of papaverine (0.4 mg), a significant increase in the ICP occurred from resting (8.9 +/- 1.8 mm Hg) to a peak at 57.5 +/- 9.9 mm Hg and persisted for 22.3 +/- 6.7 minutes (p < 0.05). The latter application significantly decreased MABP (22.3 +/- 3.1 mm Hg; p < 0.05). CONCLUSIONS: Intraurethral administration of papaverine does not seem to be an alternative to other erectile dysfunction treatment modalities. However, further studies on animals are necessary at higher concentrations or in combination with other mucosal enhancers to increase the effect of intraurethral administration of papaverine.

Animals↗
PubMed2000

Aggressive management of aneurysmal subarachnoid haemorrhage based on a papaverine angioplasty protocol.

The aim of this study was to analyse the results of intensive therapy unit management of aneurysmal subarachnoid haemorrhage incorporating angioplasty in the protocol. Two hundred consecutive patients were treated using a detailed protocol that included nimodipine, early aneurysm repair, and surveillance angiography. Angiography was performed on days 5 to 7 (or when the clinical state suggested the presence of vasospasm). If angiographic vasospasm was identified, irrespective of whether clinical vasospasm was present or absent, papaverine was selectively administered. In patients with vasospasm blood pressure was elevated to 160-180 mmHg and selective papaverine administration was repeated daily until vasospasm resolved. In cases requiring more frequent administration of papaverine, or in whom papaverine failed to adequately reverse spasm, balloon angioplasty was considered and for clinically refractory cases barbiturate coma was introduced. 43% of patients underwent papaverine administration and of these the average number of separate papaverine procedures was four (maximum 23). 26% of patients developed neurological deficits though to be due to vasospasm whilst 17% underwent papaverine angioplasty without clinical signs of vasospasm. Twelve patients (6%) were entered into barbiturate coma. There was a 5.5% mortality and no difference in outcome between patients who developed angiographic vasospasm and those who did not. For those developing clinical vasospasm, 71% were independent and 10% were dead at follow up compared with 84% reaching independent grades and 4% dead in those not developing clinical vasospasm. These differences failed to reach a significant difference. The average Intensive Therapy Unit stay for aneurysmal subarachnoid haemorrhage patients was 13.1 days with a mean cost to the hospital of $AUD 24,379. This protocol appears to be both a clinically and cost effective method of managing aneurysmal subarachnoid haemorrhage.

Angioplasty, Balloon↗
PubMed1989

Inhibitory effect of papaverine on HIV replication in vitro.

The ability of papaverine to inhibit human immunodeficiency virus (HIV) replication in H9 cell line and in peripheral blood mononuclear cell (PBMC) culture was examined. HIV-infected H9 cells were exposed to different concentrations of papaverine for 20 days. Reverse transcriptase (RT) activity and the presence of p24 in the supernatant were determined to assess the level of viral replication in treated and control cultures. The most effective concentration of papaverine in the culture medium was 10 micrograms/ml, a dose that did not significantly affect cell proliferation. At this drug concentration the treatment resulted in no RT activity or p24 expression in the supernatant and no virus antigen detection at the cellular level as demonstrated by Western blot (WB) analysis. The activity of the drug occurred in a short period of time (60 hours) as shown by radioimmunoprecipitation (RIP) assay and affected the synthesis of the env precursor protein gp160. The drug was also effective in inhibiting HIV replication in PBMC cultures and influenced specific viral markers, namely, RT and p24. Evidence of the efficacy of papaverine treatment was enforced by the finding in the treated PBMC cultures, compared with the untreated ones, of a reduced percentage of cells forming syncitia and of the inhibition of the virus-induced decrease in the number of cells. When an equal number of virus-infected H9 cells exposed or unexposed to papaverine was analyzed for HIV-specific proteins, a marked decrease in the expression of the viral proteins was observed in the treated cultures. At the same time, one cellular protein of molecular weight 69,000 was not inhibited by papaverine. This may indicate that, at least for one protein, synthesis may not be affected by the drug. Our data suggest that papaverine merits attention as a possible nontoxic candidate for the treatment of HIV infection.

Blotting, Western↗
PubMed1993

Intracoronary papaverine but not adenosine reduces regional ventricular function.

OBJECTIVES: Whether intracoronary papaverine or adenosine leads to reductions in regional left ventricular function was tested. METHODS: Fifteen anaesthetised dogs were prepared to record aortic pressure, left ventricular pressure dP/dt, electrocardiogram, regional ventricular shortening, and phasic and mean left circumflex coronary blood flow, and to give intracoronary boluses of papaverine (2, 4, or 6 mg) or adenosine (0.37 and 1.87 mg). RESULTS: Injected doses were chosen to mimic those given in the clinical setting. Papaverine (6 mg) reduced aortic pressure (mean 96(SD 17) to 89(18) mm Hg; p < 0.05), segmental shortening of the infused left circumflex zone (12(5) to 7(9)%; p < 0.05), and area of the pressure-length loop of the infused zone (120(71) to 53(47) mm.mm Hg; p < 0.05). Papaverine increased coronary blood flow (48(25) to 259(95) ml.min-1; p < 0.05), coronary vascular conductance (0.40(0.20) to 2.93(0.94) ml.mm Hg-1.min-1; p < 0.05), heart rate (88(27) to 100(28) beats.min-1; p < 0.05), and the segmental shortening (17(6) to 19(3)% p < 0.05) and area of the pressure-length loop (130(32) to 177(33) mm.mm Hg; p < 0.05) of the non-infused left anterior descending region. The hyperaemia elicited by papaverine was greater than that of reactive hyperaemia (p = 0.008). Papaverine also increased the QT interval corrected for heart rate (0.35(0.04) to 0.45(0.05) s; p < 0.05). When adenosine was given, coronary blood flow and coronary vascular conductance were increased to similar degrees as those during reactive hyperaemia (41(12) to 210(75) ml.min-1 and 0.46(0.14) to 2.43(0.83) mm Hg.ml-1.min-1, respectively; NS). No effects on segmental shortening or the area of the pressure-length loop in either zone were found. Also, adenosine had no effect on the QT interval. CONCLUSIONS: These adverse effects of intracoronary papaverine have important implications in its use in patients, particularly in those in whom abnormal cardiac function already exists. Adenosine, on the other hand, seems to be without deleterious effects.

Adenosine↗
PubMed1998

Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm.

OBJECTIVE: We examined the therapeutic benefits of intra-arterially administered papaverine for treatment of symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). Recent advances in microcatheter technology have facilitated endovascular approaches to vessels experiencing vasospasm after SAH. However, despite numerous encouraging anecdotal reports, no rigorous examination of the efficacy of these procedures has been published. Intra-arterial infusion of papaverine has become part of the standard management of vasospasm at some centers. METHODS: We examined a series of 31 patients undergoing papaverine infusion for the treatment of symptomatic vasospasm after SAH. The patients were a subgroup of the series enrolled in the North American Trial of Tirilizad for Aneurysmal Subarachnoid Hemorrhage. These individuals were matched with patients from the same trial who exhibited similar clinical characteristics (including the degree of vasospasm and the modified Glasgow Coma Scale scores measured at the time of admission and on the day of papaverine infusion) but received medical management alone for vasospasm. RESULTS: Logistic regression analysis comparing these two groups showed no statistical difference in the 3-month Glasgow Outcome Scale scores between patients receiving papaverine and control subjects (58% favorable outcomes for control subjects versus 45% for patients receiving papaverine). CONCLUSION: Although isolated series documenting clinical successes have prompted the increased use of papaverine as a treatment for vasospasm after SAH, this series suggests that, as it is currently being used, the drug does not provide added benefits, compared with medical treatment of vasospasm alone. This result does not preclude the possibility that alterations in the timing of or indications for drug treatment might produce beneficial effects.

Adult↗
PubMed1975

Papaverine: its effects on cyclic AMP in vitro and psoriasis in vivo.

Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 x 10-4 m) produced a 210percent increase (.02 smaller than p smaller than .05) in epidermal cyclic AMP levels in vitro. Therefore, 1 percent papaverine cream (approximately 2.7 x 10-2m papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a soriatic lesion. A double-blind comparison of 1 percent papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81 percent (p=0.011) of those showing a response in the center of the lesion and 77 percent (p=0.046) of those improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments.

Animals↗
PubMed1992

Comparison of effects following the intracorporeal injection of papaverine and prostaglandin E1.

A study group of 240 impotent men receiving intracorporeal injections were divided into 2 groups: the first group received papaverine (60 mg) and the second prostaglandin E1 (PGE1 20 micrograms). The effect of the drugs was evaluated according to the onset of erection, rigidity and the duration of erection; 136 patients were treated with papaverine and 104 with PGE1. The onset of action in these groups was 6.42 +/- 5.39 vs 10.14 +/- 5.41 min; the rigidity score was 3.37 +/- 0.89 vs 3.60 +/- 1.10 and the duration of erection was 49.56 +/- 62.56 vs 63.60 +/- 44.57 min respectively. There was a significant difference in the onset of action (PGE1 was slower than papaverine) and maintenance of erection (longer with PGE1 than with papaverine). Another group of 17 patients received both papaverine and PGE1. The effects of papaverine were better in 4 cases, worse in 5 and equal to PGE1 in 8. This study indicates that compared with papaverine, treatment with PGE1 produces a slower onset of action, a longer duration of erection and fewer side effects.

Adult↗
PubMed2003

Papaverine blocks hKv1.5 channel current and human atrial ultrarapid delayed rectifier K+ currents.

Papaverine, 1-[(3,4-dimethoxyphenyl)methyl]-6,-7-dimethoxyisoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K(+) channel (hKv1.5) cloned from human heart and stably expressed in Ltk(-) cells as well as a corresponding K(+) current (the ultrarapid delayed rectifier, I(Kur)) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time- and voltage-dependent manner with an IC(50) value of 43.4 microM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 microM) also blocked I(Kur) in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.

Animals↗
PubMed2003

Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans.

BACKGROUND: Inducing both maximal and steady-state coronary hyperemia is of clinical importance to take full advantage of fractional flow reserve measurements. The present study compares different dosages and routes of administration of adenosine 5'-triphosphate (ATP), adenosine, contrast medium, and papaverine regarding their potential to achieve both maximal and steady-state hyperemia. METHODS AND RESULTS: In 21 patients with an isolated coronary stenosis, coronary vasodilation was induced successively by papaverine (20 mg intracoronary), adenosine (20 and 40 microg intracoronary), ATP (20 and 40 microg intracoronary), iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140 and 180 microg x kg(-1) x min(-1)), or adenosine or ATP through a femoral vein (140 and 180 microg x kg(-1) x min(-1)). Because vessel dimensions did not change, the ratio of distal coronary pressure (Pd) to aortic pressure (Pa) was used as an index of myocardial resistance. Pd/Pa was 0.77+/-0.21 at rest and decreased to 0.61+/-0.21 after papaverine. Pd/Pa decreased to a similar level with all other vasodilators, except with contrast medium (0.68+/-0.21; P<0.01 versus papaverine). Steady-state hyperemia could only be obtained by intracoronary papaverine and by intravenous ATP or adenosine. In another 23 patients, an intravenous infusion of ATP was varied from 0 to 280 microg x kg(-1) x min(-1). At doses >140 microg x kg(-1) x min(-1), there was neither a further decrease in Pd/Pa ratio nor a further increase in coronary flow velocities. CONCLUSIONS: Provided sufficient dosages are used, ATP, adenosine, and papaverine (but not contrast medium) induce maximal hyperemia and are therefore suitable to assess fractional flow reserve. Only intracoronary papaverine and intravenous ATP or adenosine induce steady-state hyperemia enabling a pressure pullback maneuver that is useful in assessing diffuse coronary atherosclerosis.

Adenosine↗
PubMed1980

Papaverine-induced inhibition of electrical and mechanical activity and calcium movements of rat ileal smooth muscle.

1. Papaverine, in the concentration range 50-150 microM, inhibited rhythmic spontaneous contraction and caused relaxation of KCl-induced contractures of rat ileal smooth muscle. 2. Spontaneous slow waves and spikes declined at low papaverine concentrations. 3. The normal 45Ca uptake of the ileum was reduced by papaverin. Although papaverine caused only a small inhibition of normal 45Ca efflux from the ileum, it strongly inhibited the KCl-induced stimulation of 45Ca efflux. 4. Calcium uptake by the isolated ileal smooth-muscle microsomal fraction was slightly increased by papaverine, but mitochondrial calcium uptake was unaffected. 5. Ileal smooth muscle incubated in calcium-free media showed little response to either the reintroduction of calcium or KCl in the presence of papaverine. 6. It is suggested that the inhibitory actions of papaverine on ileal smooth muscle result from a blockade of the calcium influx which triggers the excitation-contraction coupling sequence.

Animals↗
PubMed1985

Mechanism of relaxant action of papaverine. VI. Sodium ion dependence of its effect on 45Ca-efflux in guinea-pig taenia coli.

The present study was undertaken to investigate the roles of sodium ion and the cyclic AMP system in the relaxant effect of papaverine. The effects of papaverine on the 45Ca-efflux and the mechanical activity of guinea-pig taenia coli were tested in solutions in which the concentration of sodium ion was varied and compared with those of dibutyryl cyclic AMP. Papaverine dose-dependently caused an acceleration of 45Ca-efflux and the synchronous relaxation of a depolarized preparation in normal bathing solution. Dibutyryl cyclic AMP mimicked these effects of papaverine. In Na-free solution, papaverine lost its ability to accelerate the 45Ca-efflux, and its relaxant activity was markedly reduced, while dibutyryl cyclic AMP had neither an effect on the 45Ca-efflux nor an effect on the muscle relaxation in Na-free solution. Reintroduction of a small amount of sodium ion to the solution, however, recovered these effects of papaverine and dibutyryl cyclic AMP on the 45Ca-efflux and the muscle relaxation. These findings indicate that the relaxant effect of papaverine may be in part due to an increase in cyclic AMP-mediated Ca-efflux which requires the presence of external sodium ion. The sodium ion dependence of this Ca-efflux process was also discussed.

Animals↗