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A Jurkiewicz

Publications and source records attributed to A Jurkiewicz.

At least 19 recordsLinked to original sources
PubMed1992

Increased density of alpha-adrenoceptors in vas deferens of spontaneously hypertensive rats (SHR), indicated by functional and receptor binding studies.

Pharmacological parameters were determined from contractile responses mediated by alpha-adrenoceptors in vas deferens from spontaneously hypertensive rats (SHR) and corresponding normotensive controls, Wistar Kyoto rats (WKY), and compared with data obtained from radioligand binding assays. Contractile responses induced in longitudinal and circular muscle layers by the alpha-adrenoceptor agonist noradrenaline (NA) and by barium chloride were recorded as described previously. In both muscle layers the maximal effects induced by NA, but not by BaCl2, were significantly greater in SHR. As a consequence, the relative responsiveness ratio (rho) for the alpha-adrenoceptor was also larger for SHR than for WKY. NA-induced contractions of both muscle layers were competitively antagonized by indoramine. The pA2 values for indoramine and pD2 values for NA were the same in SHR and WKY, indicating that alpha-adrenoceptor affinity was not changed in SHR. Additionally, binding studies with the alpha-adrenoceptor ligand [3H]WB4101 revealed that Bmax values were greater in the vas deferens of SHR, whereas Kd values were not significantly different from those of WKY controls. In summary, although differences could not be detected for affinity-related parameters, a greater density of alpha-adrenoceptors was shown for SHR in receptor binding studies and this was corroborated by functional studies.

Animals↗
PubMed1992

In vitro denervation of the rat vas deferens through hypothermic storage.

1. The rat vas deferens was excised, stored at 4-6 degrees C and tested after 24, 48, 72 or 96 h for its contractile activity and for the presence of innervation. 2. The maximal contractile capacity of the vas, tested through cumulative concentrations of barium chloride (3 x 10(-2) M) was progressively reduced from about 110 mm to about 63 mm after 72 h, without further decay after 96 h. Spontaneous rhythmic contractions were practically absent. 3. A loss of endogenous pools of catecholamines was indicated by four parameters: (a) a decline of about 80% after 24 h and of more than 95% after 48 h of the contractile effect of the indirect sympathomimetic agonist tyramine; (b) a fall of about 20%, 50% and 85% on the concentration of noradrenaline, respectively after 24, 48 and 72 h; (c) a fall of about 25% and 90% after respectively 24 and 48 h, of the activity of dopamine-beta-hydroxylase (DBH); (d) a decline of noradrenaline-induced histofluorescence on cross sections of the vas. 4. A loss of neuronal uptake capacity was indicated by: (a) a progressive variation of the apparent affinity for adrenaline, expressed as pD2 values, that increased by about 1.5 log units (corresponding to a 30 fold potentiation) after 72 h, and (b) a reduction of the ability of cocaine to potentiate the contractile effects of adrenaline. 5. The pD2 values for barium chloride, 5-hydroxytryptamine (5-HT) and histamine were not significantly changed, while the corresponding value for acetylcholine was slightly but significantly reduced by about 0.8 log units. 6. The maximal heights of concentration-response curves for noradrenaline, acetylcholine, histamine and 5-HT were reduced by 42-66% in relation to controls. However, when this reduction was measured in relation to the corresponding barium effect, by means of the relative responsiveness ratio (p), a small though significant increase was observed for noradrenaline, and a fall for the other drugs.7. It is concluded that: (1) the values for the various biochemical and pharmacological parameters decline at different rates, though revealing altogether that denervation is completed by at least 85% after 72 h of hypothermic storage; (2) two of the results, i.e., the lack of spontaneous rhythmic contractions and the lack of increased contractile effects for acetylcholine, 5-HT and histamine, indicate that in these conditions the vas is devoid of the so-called nonspecific signs of denervation.

Acetylcholine↗
PubMed1992

Low dihydropyridine receptor density in vasa deferentia of castrated rats.

Radioligand binding studies in crude membrane preparations of vasa deferentia of normal rats, with the 1,4-dihydropyridine (+)-[3H]-PN200-110 (isradipine) showed typical saturation isotherms. The binding exhibited a KD of 259 +/- 60 pM and Bmax of 144 +/- 20 fmol mg-1 protein. The low KD and the stereoselective displacement of (+)-[3H]-PN200-110 binding by (+)- and (-)-PN200-110 and by nifedipine suggests that these tissues contain dihydropyridine receptors probably coupled to voltage-sensitive, L-type calcium channels. In membrane preparations from vasa deferentia from rats castrated 30 days previously the maximum specific binding was 25 +/- 10 fmol mg-1 protein, representing only 11% of total binding; thus, the calculation of reliable KD values was not feasible. These findings suggest that a testicular hormone, possibly testosterone, plays an important role in the regulation of dihydropyridine-sensitive, voltage-dependent calcium channels in the rat vas deferens.

Animals↗
PubMed1992

Partial hindrance by beta-adrenoceptors of the antagonism of prazosin against adrenoceptor agonists in rat caecum.

The relaxation of the carbachol-contracted rat isolated caecum by noradrenaline (NA), adrenaline (A) and isoproterenol (I) was investigated, to identify the pharmacological receptors involved. The organs were pretreated with cocaine to block neuronal uptake. The relative potencies of the three agonists were I >> A > or = NA, indicating the presence of beta-adrenoceptors. However, the shift of concentration-response curves by the beta-adrenoceptor antagonist propranolol varied according to the agonist used, suggesting the presence of distorting factors. Initial attempts to verify if alpha-adrenoceptors were involved, by using the alpha-adrenoceptor antagonist prazosin, were unsuccessful, since the shifts of the concentration-response curves were small and were not concentration dependent, leading to Schild lines with slopes significantly lower than unity. When the experiments with prazosin were repeated in the presence of large concentration of propranolol (10(-5) mol/l) to block beta-adrenoceptors, the relative potencies were changed to NA > A > or = I, reflecting the presence of alpha-adrenoceptors. In addition, the shifts induced by prazosin against A lead to Schild lines with slopes not different from 1.0. It is concluded that alpha-adrenoceptors are also present in the caecum, but its presence can only be clearly disclosed after blockade of beta-adrenoceptors. The results are discussed in relation to other situations known to hinder the determination of relative potencies and competitive antagonism, as for instance the removal of agonist from the vicinity of receptors by drug uptake mechanisms.

Adrenergic Agonists↗
PubMed1991

Reinnervation of the transplanted vas deferens: differential recovery of various biochemical and pharmacological parameters.

Biochemical and pharmacological parameters were used to follow the innervation characteristics of the rat was deferens transplanted (T) to the caecum. After about 5 months, a regeneration of autonomic nerves was clearly shown: first, by a complete recovery of neuronal uptake, indicated by: a) potentiation by cocaine of epinephrine (EPI) dose-response curves (T = 1.47 +/- 0.25, controls (C) = 1.50 +/- 0.14 log units); b) reversion to normal levels of pD2 values for norepinephrine (NE) and EPI (T = 6.6 +/- 0.1; 7.0 +/- 0.1, and C = 6.4 +/- 0.1; 6.9 +/- 0.1, respectively); second, a partial restoration of nerve terminals, and corresponding pools of NE, which was seen through histofluorescence and was indicated by a percent increase of: a) NE content, 47% (T = 3.8 +/- 0.8, C = 8.5 +/- 0.7 micrograms/g); b) dopamine-beta-hydroxylase (DBH) activity, 37% (T = 136 +/- 80, C = 364 +/- 15 nmol(hr.g); c) release of NE by 57 mM-potassium, 23% (T = 33.0 +/- 12.0, C = 147 +/- 14 ng/g. 5 min). Yet, two peculiarities of denervated organs remained practically unchanged even after 5-month transplantation: NE supersensitivity, measured by the relative responsiveness (rho) ratio (T = 0.96 +/- 0.02, C = 0.69 +/- 0.03), and tyramine-induced contraction, that was recovered by only 14% (T = 10.0 +/- 2.4, C = 72.0 +/- 3.5 mm). This differential recovery of the aforementioned parameters is discussed in the light of receptor mechanisms and functional changes following reinnervation.

Animals↗
PubMed1991

Release of contractile agents from rat vas deferens by clonidine.

Clonidine induces contractile effects on the isolated rat vas deferens, but not on rat uterus or guinea-pig ileum. However, we have observed that if clonidine is incubated for about 10 min with a nutrient solution containing an isolated rat vas deferens, the resulting solution can contract an isolated rat uterus, or guinea-pig ileum indicating the involvement of a substance released from the vas. This contractile effect was partially reduced by naloxone and by serotonin antagonists, and by using a denervated vas, indicating that opioids, serotonin and eventually other substances released from nerve tissue of the vas can be involved.

Animals↗
PubMed1991

Different mechanisms of action of agents acting on beta-adrenoceptors in barium-stimulated and electrically-stimulated rat vas deferens.

1. The relaxation induced by beta-adrenoceptor agonists in rat vas deferens was examined under two different experimental conditions: on electrically-induced twitch responses (35 V, 3 ms, 0.07 Hz), and on contractions induced by single doses of barium chloride (300 microM). The experiments were performed in vasa of reserpine-treated rats, after blockade of alpha-adrenoceptors and extraneuronal uptake with dibenamine (10 microM, 30 min), and neuronal uptake with cocaine (10 microM). 2. When twitch responses were used, the values of pD2, interpolated from cumulative concentration-response curves for isoprenaline (Iso), adrenaline (Ad), and noradrenaline (NA) showed a rank order of potency consistent with the presence of beta 2-adrenoceptors (Iso greater than Ad much greater than NA). 3. When twitch responses were used, the non-selective beta-antagonist, propranolol, caused a concentration-dependent parallel shift to the right of Iso concentration-response curves. Similar shifts were obtained by use of the beta 2-antagonist, isopropylmethoxamine (IMA), and higher doses of the beta 1-antagonist, practolol, according to the expectations from receptor occupation theory. Practolol presented the lowest value of pKB, 5.03, corroborating the presence of beta 2-adrenoceptors. 4. When twitch responses were used, and Ad or NA employed instead of Iso, the antagonists produced shifts of concentration-response curves which were smaller than expected from theory, precluding the determination of pKB values. This indicates that other mechanisms are involved besides an interaction with a single population of postsynaptic beta 2-adrenoceptors. 5. When barium chloride was used instead of twitch responses, although the potencies of Iso and Ad were increased respectively by about 30 fold and 5 fold, the rank order of potency was still consistent with an interaction with beta 2-adrenoceptors. In addition, the antagonists produced parallel and concentrationdependent shifts of the curves of all the agonists, as expected from receptor theory. The values of pKB for a given antagonist were not modified by interchanging the agonists used, indicating a typical interaction with a single population of beta 2-adrenoceptors. When compared to the field-stimulated vas, the values of pKB for propranolol and IMA against isoprenaline were respectively 1.3 and 0.6 log units larger. These results suggest the beta l-adrenoceptor agents act by different mechanisms of action in barium-stimulated and electrically-stimulated vas. 6. It is suggested that when barium is used, the effects of agents acting on beta l-adrenoceptors are mediated only by postsynaptic beta 2-receptors, while other complicating factors, probably nerve-dependent presynaptic mechanisms, may be involved with electrical stimulation.

Adrenergic beta-Agonists↗
PubMed1991

Comparison of the effect of calcium withdrawal from the medium and of blockade of extracellular calcium entry by isradipine on the contractile responses of the isolated rat stomach.

The role of calcium in drug-induced contractions of rat gastric fundus strips was evaluated by determining the effect of two procedures on the dose-response curves of agonists: a) removal of calcium from the nutrient solution and b) blockade of calcium channels with the dihydropyridine isradipine. Gastric strips were obtained from adult Wistar rats and suspended in Tyrode solution at 37 degrees C for contraction studies. Dose-response curves for carbachol (CCh), serotonin (5-HT), KCl and BaCl2 were constructed under the two conditions described above. A complete blockade of contractile effects was observed for 5-HT and KCl 60 min after calcium withdrawal or after using 3 nM (45 min) of the calcium antagonist. A lower dose of antagonist or a shorter incubation in calcium-free solution caused a partial decrease of dose-response curves, added to a 30-fold shift to the right after the calcium antagonist (1 nM), or a larger than 100-fold shift 3 min after calcium removal. In contrast, dose-response curves for CCh and BaCl2 were not significantly affected by either type of treatment. It is concluded that 5-HT and KCl utilize extracellular sources of calcium, whereas CCh or BaCl2 depends on a tightly-bound calcium pool in this preparation.

Animals↗
PubMed1990

Dissociation constants and relative efficacies estimated from the functional antagonism of beta-adrenoceptor agonists on transmural stimulation in rat vas deferens.

In rat vas deferens, the beta-adrenoceptor agonists, isoprenaline, salbutamol, terbutaline and fenoterol, inhibited the contractions elicited by transmural electrical stimuli to an extent which depended on voltage magnitude. The dose-response curves for these agonists were shifted slightly to the right when the amplitude of the twitch was increased up to twice its original size. Consequently, the values of pD2 for the respective agonists obtained with a '50% twitch' and a '100% twitch' were: 7.6 and 7.5, 6.8 and 6.6, 6.2 and 6.0, 7.6 and 7.4. In addition, the maximal effects of the agonists were significantly reduced (by 13-18%). The values of other parameters for the same agonists, calculated according to a model for functional antagonism, were: negative log of dissociation constants (pKa): 7.2, 6.3, 6.2 and 7.2; percent receptors occupied to induce a half-maximal effect (y50): 42, 46, 63, and 53; relative intrinsic efficacy (er): 1.0, 0.9, 0.7, and 0.8. The usefulness of this type of functional antagonism as an alternative method for the estimation of drug-receptor parameters is discussed in the light of receptor theory.

Adrenergic beta-Agonists↗
PubMed1990

A double perfusion system with two-channel recording for the simultaneous study of the contractile responses of the circular and longitudinal smooth muscle layers of the rat vas deferens.

A device for double perfusion of the vas deferens externally and through the lumen is described in detail. The perfusion system allows the simultaneous recording of drug-induced or spontaneous contractions of the circular and longitudinal smooth muscle layers of the organ. Isometric contractions of the longitudinal (external) layer are recorded through a tension transducer. The contractions of the circular (internal) smooth muscle layer are recorded as changes of the pressure of internal perfusion. Therefore, four different effects can be recorded for a given concentration of agonist by combining the variables related to the route of perfusion (external or internal) and type of muscle (longitudinal or circular). In addition, antagonism or synergism can be studied by simultaneously perfusing a second drug. Results can be expressed as single records or as mean concentration-response curves from which drug-receptor parameters can be directly or indirectly obtained. The importance of employing this method for the analysis of some less usual problems related to the mechanism of drug action is discussed.

Animals↗
PubMed1989

Contractile responses of the guinea-pig vas deferens to the combination of vanadium ions with ouabain.

1. Vanadate and vanadyl ions (10(-5)-10(-2) M) induced dose-dependent rhythmic contractions of the vas deferens of reserpine-treated guinea-pigs. The Na, K-ATPase blocker ouabain (10(-5)-10(-3) M) induced similar, though smaller, effects. Experiments were performed to verify if these effects are due to an interaction with the same receptor population. 2. Ouabain caused a striking potentiation of vanadium effects, which was also observed in denervated organs, indicating that a release of neuronal substances is not involved in potentiation. Similar potentiations were observed by combining vanadium with K-free solutions instead of ouabain, corroborating the involvement of the latter drug with Na, K, ATPase. 3. From the analysis of time-response and concentration-response curves, there are at least three indications that vanadium and ouabain interact with different sites: (a) the combined effect of both agonists was several times higher than the corresponding isolated effects; (b) the combined effect, expected to be independent of the order of addition of the agonist, was higher if vanadium was added before, than after ouabain; (c) the combined effect on the time elapsed between the addition of the two agonists, being higher if an interval of at least 10 min was allowed between vanadium and ouabain additions. 4. In conclusion, our results do not support the hypothesis that vanadium compounds and ouabain have a similar mechanism of action for the contraction induced in guinea-pig vas deferens.

Animals↗
PubMed1988

Some pharmacological properties of the circular smooth muscle layer of the rat vas deferens.

Vas deferens preparations were perfused in-vitro through the lumen and externally with a modified Tyrode solution alone or containing drugs. Contractions of the circular (internal) smooth muscle layer were recorded as changes in the pressure of internal perfusion. Contractions of the longitudinal (external) layer were simultaneously recorded through a tension transducer. When the organ was perfused through the lumen, the circular layer contracted after addition of methacholine (pD2 = 4.13), and noradrenaline (pD2 = 5.00), and relaxed after addition of isoprenaline (pD2 = 5.22). These effects were also observed when the drugs were perfused externally, although with lower values of pD2 for noradrenaline and methacholine. The circular fibres were less sensitive when compared with the longitudinal fibres perfused externally with the above agonists. Methacholine-induced contractions of the circular layer were competitively antagonized by atropine (pA2 = 8.53), indicating the presence of muscarinic receptors. The effects induced by noradrenaline and isoprenaline were antagonized by indoramin (pA2 = 7.78), and timolol (pA2 = 8.68), respectively, indicating the presence of alpha- and beta-adrenoceptors. The effect of noradrenaline was potentiated by cocaine and denervation, indicating the presence of neuronal uptake, and by corticosterone, indicating the presence of extraneuronal uptake in the circular layer.

Animals↗
PubMed1986

Renal haemodynamics in spontaneously hypertensive rats with superficial glomeruli.

Spontaneously hypertensive rats (SHR) were mated with Munich-Wistar rats (MW), and the F1 hybrids were called Escola Paulista de Medicina (EPM) rats. The EPM rats present spontaneous hypertension and superficial glomeruli, allowing a study of glomerular haemodynamics. Mean whole kidney (GFR) and single nephron glomerular filtration rate (SNGFR), and mean total and glomerular plasma flow, were similar in EPM and MW rats. However, a higher glomerular capillary hydraulic pressure and a reduced ultrafiltration coefficient (Kf) of EPM rats were observed. The glomerular hypertension may be the cause of low Kf, a possible initial lesion of glomerular sclerosis. When mean arterial pressure levels were reduced to about 90 mmHg, a maintenance of SNGFR, with a 40% reduction in GFR, in EPM rats were achieved, suggesting an autoregulatory mechanism in the superficial but not in the juxtamedullary nephrons. The decrease on urinary sodium excretion (UNaV) in this condition, which was also lower than in MW rats, showed an impaired sodium handling by EPM kidneys, a possible role in the hypertension genesis. Thus, the data suggest that EPM rats can be a useful model for glomerular haemodynamics and microcirculatory studies in the spontaneously hypertensive state.

Animals↗
PubMed1985

Evidence for multiple sources of calcium involved on the contractile effects of agonists in the dog uterus. Influence of ovarian sexual hormones.

We compared the characteristics of Ca2+ pools involved in the contractile effect of acetylcholine (Ach), histamine (Hist), oxytocin (Oxy) and barium (Ba2+) in prepuberal untreated or estrogen plus progesterone dominated uteri. After Ca2+ (0.2 mM) withdrawal different rates of decay for cited agonists were observed. If Ca2+ concentration was increased to 2.0 mM before the Ca2+ withdrawal, the t 1/2 for Ach and Hist were markedly increased. Hormonal treatment significantly increase the rate of decay for all agonists except for Ba2+ independent of the initial Ca2+ concentration, suggesting that in this condition the tightly bound Ca2+ is absent.

Acetylcholine↗
PubMed1985

Simultaneous measurement of contractile effects in the circular and longitudinal smooth muscle of the rat vas deferens by drugs perfused externally or via the lumen.

The effects of noradrenaline and barium chloride were studied in the rat isolated vas deferens by perfusion of drugs either externally or through the lumen of the organ. Two effects were recorded simultaneously in the same preparation: (a) isometric contractions, due to the tension elicited by drugs on the external (longitudinal) smooth muscle layer and (b) pressure of internal perfusion, due to contractions of the internal (circular) smooth muscle layer. It was found with the longitudinal muscle that: (a) the potency, expressed as pD2 values, and the maximum response to noradrenaline were lower if the drug was perfused internally rather than externally; (b) the differences in maximum effects were pronounced on the prostatic half but were not observed on the epididymal half; (c) the maximum response obtained by internal perfusion could be increased by simultaneously adding the same dose of drug externally; (d) when barium chloride was used instead of noradrenaline no significant differences were observed on pD2 values, but differences on maximal responses were similar to that observed for noradrenaline; (e) it was possible to block completely the effect of internal or external noradrenaline on the longitudinal muscle, by perfusing external phenoxybenzamine. In these conditions the responses of the circular muscle to the agonist were only partly blocked. With the circular muscle, the differences related to internal and external perfusion were less marked than in the longitudinal muscle. However, unlike the latter, the circular layer was slightly more sensitive to drugs applied internally, in relation to pD2 values. It is suggested that the difference in pD2 values may be due to the removal of noradrenaline by the neuronal uptake process, whereas the difference in maximal effect is due to the inaccessibility of part of the receptor population when drugs are added through the lumen.

Animals↗
PubMed1985

Characteristics of spontaneously hypertensive, Wistar Kyoto and Munich Wistar rats bred in Brazil.

The breeding of imported strains of isogenic rats was started in 1981 because of the lack of experimental rat models in Brazil. The imported strains were: Spontaneously Hypertensive Rats (SHR) and their normotensive controls Wistar Kyoto Rats (WKY) from the National Institutes of Health, Bethesda, MD, and Munich Wistar (MW) rats which present superficial renal glomeruli, from Simonsen Laboratories, Gilroy, CA. Breeding of these strains was carried out without strict barriers (conventional breeding), under Standard Operating Procedures and strict inbreeding. Environmental factors such as ration, light, temperature, type of shavings and bedding, size of cages and their population were constant. Body weight growth curves were constructed for the three strains. The productivity of imported rats and local breeding colonies in 1981, 1982 and 1983 was compared on the basis of the following parameters: mean litter size, productivity of the females, pre- and post-weaning mortality, and effective yield. Systolic blood pressure was also measured for SHR and WKY rats. MW rats showed a high and relatively stable reproduction performance. The productivity of SHR and especially WKY animals declined progressively during the first three years, making the breeding of these strains of isogenic rats very difficult.

Animals↗
PubMed1979

Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs.

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.

Acetylcholine↗