Noradrenaline In Rat Vas Deferens Research Articles

Assessment of the adrenergic effects of orphenadrine in rat vas deferens.

The peripheral adrenergic effects of orphenadrine, an antiparkinsonian drug, have been evaluated in the rat vas deferens to investigate whether these properties are the same as those of other phencyclidine ligands. In the low micromolar range, orphenadrine enhanced electrically-evoked and exogenous noradrenaline contractile responses in the epididymal portion of rat vas deferens. It also induced spontaneous activity that was inhibited by prazosin (1 microM) but not by atropine (20 nM). It inhibited accumulation of [3H]noradrenaline in rat vas deferens (IC50 = 14.2+/-2.3 microM). Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (Ki = 1.05+/-0.20 microM). It can be concluded that orphenadrine, at low micromolar concentrations, interacts with the noradrenaline reuptake system inhibiting its functionality and thus potentiating the effect of noradrenaline.

Effect of D-004, a Lipid Extract from??the Cuban Royal Palm Fruit, on In??Vitro and In Vivo Effects Mediated by????-Adrenoceptors in Rats

Benign prostatic hyperplasia (BPH) is the non-malignant, uncontrolled growth of glandular and stromal elements of the prostate gland. Lipid extracts from Saw palmetto (Arecaceae) fruits are widely used to treat BPH. The Cuban royal palm (Roystonea regia) is a member of the same family. Previous studies have found that D-004, a lipid extract from the R. regia fruit, administered orally at 200-800 mg/day for 14 days, prevented testosterone- but not dihydrotestosterone-induced prostate hyperplasia in rats. To determine whether D-004 can inhibit noradrenaline (NA) [norepinephrine]- and acetylcholine (ACh)-induced smooth muscle contraction in rat vas deferens and to investigate the in vivo effects of D-004 on NA pressure-elevating effects in rats, an effect mediated by vascular alpha1-adrenoceptors. In vitro effects were investigated by adding D-004 (125-500 microg/mL) to preparations of rat vas deferens suspended in an organ bath containing Tyrode's solution, in which in vitro contractions were induced by NA or ACh. Negative and positive controls containing Tyrode's solution alone or with Saw palmetto extracts (125-500 microg/mL), respectively, were included. To assess the in vivo effects of D-004 on arterial blood pressure, rats were randomly distributed to one of five groups (ten rats/group): these consisted of a negative control group receiving the vehicle, two groups treated with D-004 (400 and 800 mg/kg) and two other groups treated with Saw palmetto (400 and 800 mg/kg). All treatments were orally administered. Rats were anaesthetised with sodium thiopental. Heart rate and blood pressure were registered in baseline conditions. Immediately afterwards, rats were injected intravenously over 5 seconds with successive doses of NA (1, 2 and 4 microg/kg) [0.1mL/100g], with 5 minutes' interval between doses. D-004 and Saw palmetto (125-500 microg/mL) significantly (p < 0.05) and dose dependently inhibited contractions induced by NA in rat vas deferens versus control. D-004 was more effective in inhibiting NA-induced contractions than Saw palmetto. The contractions induced by NA in preparations with D-004 (500 microg/mL) were weaker (p < 0.05) than in preparations containing Saw palmetto (500 microg/mL). At 125 microg/mL, D-004 inhibited the contractions induced by NA 1 and 32 x 10(-6) mol/L by 70.8% and 28.5%, respectively, and Saw palmetto by 56.2% and 10.7%, respectively. At 500 microg/mL, D-004 inhibited these contractions by 100.0% and 71.3%, and Saw palmetto by 80.0% and 42.7%, respectively. The inhibitory concentrations of 50% (IC50) for NA contractions were 148.34 (D-004) and 188.38 (Saw palmetto) microg/mL. D-004 and Saw palmetto significantly (p < 0.05) and to a similar extent inhibited ACh-induced contractions, but less effectively than contractions induced by NA, since at 125 microg/mL they were ineffective. At a dose of 800 mg/kg, but not at 400 mg/kg, D-004 and Saw palmetto inhibited the pressure-elevating effects induced with low (1 microg/kg) but not with high doses (2 and 4 microg/kg) of NA. D-004 and Saw palmetto extracts inhibited in vitro the contractile responses to NA and ACh in rat vas deferens, and were more effective in inhibiting NA than ACh contractions. The in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by NA were significant but modest. These results are preliminary as the relevance of the effects of D-004 on alpha1-adrenoceptors deserves further investigation, including comparative studies versus specific defined alpha1-adrenoceptor antagonists.

Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.

Investigation of the subtypes of α1‐adrenoceptor mediating contractions of rat aorta, vas deferens and spleen

1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) or phenylephrine in rat vas deferens, spleen and aorta, and mediating contractions to endogenous NA in rat vas deferens have been examined. 2. In rat vas deferens, the competitive antagonists prazosin, WB 4101, benoxathian and 5-methyl-urapidil inhibited contractions to NA with pA2 values of 9.26, 9.54, 9.02 and 8.43, respectively. The irreversible antagonist chloroethylclonidine (CEC) (100 microM) failed to affect contractions to NA. 3. In rat vas deferens in the presence of nifedipine (10 microM), contractions to NA were significantly attenuated and under these conditions, CEC (100 microM) significantly reduced the maximum response to NA. 4. In rat spleen, the competitive antagonists prazosin, WB 4101 and benoxathian inhibited contractions to phenylephrine with pA2 values of 9.56, 8.85 and 7.60, respectively, and 5-methyl-urapidil had a KB of 6.62. CEC (100 microM) significantly reduced the maximum contraction to phenylephrine. 5. In rat aorta, the competitive antagonists, prazosin, WB 4101, benoxathian and 5-methyl-urapidil inhibited contractions to NA with pA2 values of 9.45, 9.21, 8.55 and 8.12, respectively. CEC (100 microM) produced an approximately parallel shift in the potency of NA, without significantly reducing the maximum response. 6. In epididymal portions of rat vas deferens in the presence of nifedipine (10 microM), the isometric contraction to a single electrical pulse was significantly reduced by CEC (100 microM), and by the competitive antagonists prazosin, WB 4101, benoxathian and 5-methyl-urapidil at concentrations of 1 nM. 7. In prostatic portions of rat vas deferens, the alpha l-adrenoceptor agonist, amidephrine, produced concentration-dependent increases in the isometric contraction to a single electrical stimulus and the maximum increase in the evoked response produced by amidephrine was unaffected by CEC (100 microM).8. Contractions of rat vas deferens produced by NA (and amidephrine) are mediated predominantly by alpha lA-adrenoceptors as shown by the high potency of alpha lA-adrenoceptor selective antagonists and the lack of effect of CEC. A small CEC-sensitive response, particularly in epididymal portions, was revealed in the presence of nifedipine. Contractions of rat spleen are mediated by alpha lB-adrenoceptors since alpha 1A selective antagonists showed low potency and CEC significantly reduced the maximum contraction to phenylephrine. Contractions of rat aorta to NA are mediated by non-alpha lA, non-alpha lB-adrenoceptors, due to the high potency of the aMA-selective antagonists and sensitivity to CEC.9. The noradrenergic contraction of epididymal portions of rat vas deferens in the presence of nifedipine is CEC-sensitive, but the alpha 1 A-selective antagonists showed high potency, suggesting that this response is mediated by non-alpha lA, non-alpha 1B-adrenoceptors.10. In conclusion, at least three subtypes of functional alpha 1-adrenoceptors have been demonstrated in these studies.

Effect of naringin and naringenin on contractions induced by noradrenaline in rat vas deferens—I. Evidence for postsynaptic alpha-2 adrenergic receptor

1. 1. Naringin at all doses (2 × 10 −6, 5 × 10 −7, and 1 × 10 −7 M) significantly increased contractions induced by noradrenaline in rat vas deferens but the increments of maximal contraction were not concentration-dependent. 2. 2. In a medium containing 1 × 10 −6 M yohimbine (a selective blocker of α 2-adrenoceptor) and naringin, the curve constructed with noradrenaline decreased below the control curve. 3. 3. Naringenin (aglycone of naringin) (2 × 10 −6 and 1 × 10 −7 M) increased the contractile effect of noradrenaline and the maximal effect evoked was related to the maximal dose of naringenin. 4. 4. The α 2 antagonism produced by yohimbine in the naringenin-noradrenaline association were retained at two doses of naringenin tested and we noticed a similar behaviour when we used clonidine-noradrenaline.

On the relationship between uptake inhibition and reversal of alpha receptor blockade by propranolol

A comparative study was made between propanolol and cocaine into the relationship between uptake inhibition and the protection and reversal of alpha receptor blockade producted by beta blockers. Propanolol was shown to potentiate the responses to noradrenaline in rat vas deferens. Cocaine exhibited both protection against and reversal of alpha blockade produced by both competitive and non-competitive alpha blockers.

ChemInform Abstract: STUDIES ON THE MECHANISMS OF ACTION OF LOCAL ANESTHETICS. PART 9. N‐AMINOACYL‐β‐PHENYLALKYLAMINE STUDIES FOR THE DEVELOPMENT OF ANTIDEPRESSANTS FROM PSYCHOSTIMULANTS

AbstractDurch Umsetzung der entsprechenden β‐Phenylalkylamine mit N‐Phthalylphenylalanylchlorid und anschließender hydrazinolytischen Abspaltung der Schutzgruppe werden die Verbindungen (I) synthetisiert.