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H Majewski

Publications and source records attributed to H Majewski.

At least 37 records · Page 2Linked to original sources
PubMed1990

Prejunctional beta-adrenoceptors, angiotensin II and neuropeptide Y receptors on sympathetic nerves in mouse atria are linked to N-ethylmaleimide-susceptible G-proteins.

We used the alkylating agent N-ethylmaleimide in order to investigate G-proteins linked to release-modulating prejunctional receptors of sympathetic nerves in mouse atria incubated with [3H]-noradrenaline. The receptors tested were facilitatory beta-adrenoceptors and angiotensin II receptors and inhibitory neuropeptide Y receptors. In order to evaluate the specificity of the N-ethylmaleimide treatment, we tested N-ethylmaleimide against the second messenger pathways that are linked to beta-adrenoceptors (adenylate cyclase) and angiotensin II (protein kinase C). The results show that a 60-min preincubation with N-ethylmaleimide (3 microM) abolished the facilitatory effect of isoprenaline (0.1 microM) and angiotensin II (0.1 microM) on the stimulation-induced release of noradrenaline and reduced the inhibitory action of neuropeptide Y (0.3 microM). N-ethylmaleimide had no effect on the stimulatory action of either phorbol dibutyrate (0.01, 0.1 microM), forskolin (10 microM), or a combination of 8-bromo adenosine-3'5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). However, at a higher concentration (10 microM), N-ethylmaleimide reduced the facilitatory effect of phorbol dibutyrate (0.1 microM) and the combination of 8-bromo adenosine-3',5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). This suggests that N-ethylmaleimide at 3 microM but not 10 microM was selective for receptor-mediated modulation of noradrenaline release without directly affecting the adenylate cyclase (forskolin, 8-bromo adenosine-3',5'-monophosphate + 3-isobutyl-1-methylxanthine) or protein kinase C (phorbol dibutyrate) transduction pathways. In atria from mice pretreated with pertussis toxin (1.5 micrograms/mouse), N-ethylmaleimide preincubation (1 and 3 microM) resulted in a more pronounced reduction of the inhibitory action of neuropeptide Y (0.3 microM). The nature of this interaction is unclear. Since N-ethylmaleimide has been shown in other studies to inactivate G-proteins, the inhibitory effect of N-ethylmaleimide on prejunctional beta-adrenoceptors, angiotensin II receptors and neuropeptide Y receptors of sympathetic nerves may suggest that G-proteins are involved with these receptors, although other effects of N-ethylmaleimide on the receptor coupling processes cannot be ruled out. Moreover, it appears that the concentration of N-ethylmaleimide used is critical since a higher concentration (10 microM) resulted in non-specific effects on signal transduction mechanisms in the present experimental conditions.

Adenylate Cyclase Toxin↗
PubMed1990

Pertussis toxin attenuates angiotensin II but not beta-adrenoceptor facilitation of noradrenaline release from rat kidney cortex.

1. Angiotensin II (AII; 0.01 and 0.1 mumols/L), angiotensin I (AI, 0.1 mumols/L) and the beta-adrenoceptor agonist isoprenaline (0.1 mumols/L) all facilitated the stimulation-induced outflow of radioactivity from slices of rat kidney cortex incubated in [3H]-noradrenaline. 2. Treatment of rats with pertussis toxin (25 and 50 micrograms/kg i.v.) to inactivate G-proteins attenuated the facilitation caused by AII and AI, but not that caused by isoprenaline. 3. The hypothesis that isoprenaline enhances noradrenaline release by generating AII to activate facilitatory prejunctional AII receptors is not supported by the present study. The hypothesis predicts that pertussis toxin, by inactivating the G-proteins associated with AII receptors, should have inhibited the facilitatory effect of isoprenaline. This did not occur.

Angiotensin I↗
PubMed1989

Modulation of noradrenaline release in slices of rat kidney cortex through alpha 1- and alpha 2-adrenoceptors.

Slices of rat kidney cortex were incubated in [3H]noradrenaline, then placed in a flow cell and subjected to electrical field stimulation. At a stimulation frequency of 5 Hz, both the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity from the slice. However, neither clonidine (0.1 microM) nor methoxamine (10 microM), alpha 2- and alpha 1-agonists respectively, affected the S-I outflow of radioactivity at this stimulation frequency. At a lower stimulation frequency (1 Hz), the S-I outflow of radioactivity was not affected by idazoxan or prazosin, but was inhibited by both clonidine and methoxamine. The effect of clonidine was prevented by idazoxan (0.1 microM), but not by prazosin (0.1 microM). The effect of methoxamine was abolished by prazosin (0.1 microM), but not by idazoxan (0.1 microM). The inhibitory effect of methoxamine was not prevented by the prostaglandin synthesis inhibitor indomethacin (10 microM) or the adenosine receptor antagonist 8-phenyltheophylline (1 microM) and thus was not mediated by either prostaglandins or adenosine. The results suggest that both prejunctional alpha 1- and alpha 2-adrenoceptors are directly involved in modulation of noradrenaline release from the renal sympathetic nerves of the rat.

Animals↗
PubMed1989

Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein.

Neuropeptide Y (30-1000 nmol/l) significantly inhibited the fractional stimulation-induced outflow of radioactivity from mouse atria preincubated with [3H]-noradrenaline. The inhibitory effect of neuropeptide Y was observed at all frequencies tested (2, 5 and 10 Hz) as well as after alpha-adrenoceptor blockade with phentolamine (1 mumol/l). A combination of 8-bromo adenosine cyclic-3'-5'-monophosphate (90 or 270 mumol/l) with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (100 mumol/l) was used to saturate maximally the adenylate cyclase system and these drug combinations significantly enhanced the stimulation-induced outflow of radioactivity. However, neuropeptide Y inhibited the stimulation-induced outflow in the presence of these drugs, suggesting that the inhibitory effect of neuropeptide Y was not due to decreasing endogenous cyclic AMP formation. Finally, atria from mice treated with pertussis toxin were used. In this case, the inhibitory effect of neuropeptide Y on the stimulation-induced outflow of radioactivity was still observed suggesting that inhibitory prejunctional neuropeptide Y receptors are not coupled to a pertussis toxin-susceptible G protein.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Beta-adrenoceptor blockade and sympathetic neurotransmission in the pithed rat.

The effects of the beta 1-adrenoceptor blocking drug atenolol and the beta 2-adrenoceptor blocking drug ICI 118551 (ICI, Melbourne, Australia) on noradrenaline release and blood pressure were investigated using the pithed rat, which was subjected to continuous electrical stimulation of the spinal sympathetic outflow (pulses at 3 Hz). This stimulation increased blood pressure but not heart rate. The noradrenaline release rate was calculated by infusing [3H] noradrenaline and measuring the steady-state concentrations of both endogenous and infused noradrenaline. Atenolol (0.2 mg/kg bolus plus 0.1 mg/kg per h, intra-arterially) had no effect on the noradrenaline release rate or heart rate, but significantly decreased blood pressure. On the other hand, ICI 118551 (0.2 mg/kg bolus plus 0.1 mg/kg per h. intra-arterially) had no significant effect on blood pressure or heart rate, but did inhibit the noradrenaline release rate. The sympathoinhibitory effect of ICI 118551 was not observed in animals which had been adrenal medullectomized, suggesting that its effect on noradrenaline release was due to blockade of activation of facilitatory prejunctional beta 2-adrenoceptors by adrenaline. The reduced noradrenaline release in the presence of ICI 118551 was not accompanied by a reduction in blood pressure. This may be because ICI 118551 also blocked vasodilatory beta 2-adrenoceptors on vascular smooth muscle. Indeed, in unstimulated pithed rats, infusions of adrenaline which were non-pressor were found to be pressor after ICI 118551 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1989

Angiotensin II and noradrenergic transmission in the pithed rat.

The norepinephrine (NE) release rate, determined in the pithed rat with stimulated sympathetic outflow (3 Hz), was calculated from the steady-state concentrations of endogenous NE and [3H]NE in the central venous pool after infusion of [3H]NE intraarterially (i.a.). This technique appropriately corrects for NE metabolism and disposition since the [3H]NE closely follows the removal path of neuronally released NE. Infusion of angiotensin II (AII) [0.1 microgram/kg/min, intravenously (i.v.)] failed to increase the NE release rate. A higher rate of infusion of AII (1.0 microgram/kg/min, i.v.) markedly increased the NE release rate. The converting enzyme inhibitor captopril (1 mg/kg, i.v.) and the AII-receptor blocking drug saralasin (10 micrograms/kg/min, i.v.) decreased the NE release rate, indicating a tonic activation of facilitatory prejunctional AII receptors at sympathetic nerve endings. After bilateral nephrectomy, captopril and saralasin did not decrease the NE release rate. This suggests that renin release from the kidney is the primary determinant of AII effects and that local tissue generation of AII is not important Other differences were observed in nephrectomized rats: AII (0.1 microgram/kg/min, i.v.), in contrast to its lack of effect in rats with kidneys, increased the NE release rate. This suggests that the lack of effect of AII (0.1 microgram/kg/min, i.v.) on NE release in rats with kidneys may occur because facilitatory prejunctional AII receptors are maximally activated by endogenous AII.

Angiotensin II↗
PubMed1989

Facilitation of noradrenaline release by isoprenaline in rat isolated atria does not involve angiotensin II formation.

1. Rat isolated atria were incubated with 3H-noradrenaline and the intramural sympathetic nerves were stimulated at 2 Hz for 60 s. The stimulation-induced (SI) efflux of radioactivity was used as an index of release of transmitter noradrenaline. 2. Isoprenaline (0.1 mumol/L) alone did not increase noradrenaline release. Cocaine (30 mumol/L) produced a 73% increase in the stimulation-induced release of noradrenaline. In the presence of cocaine, isoprenaline enhanced noradrenaline release by 22%. 3. In the presence of cocaine, both angiotensin I (0.3 mumol/L) and angiotensin II (0.3 mumol/L) produced almost two-fold enhancements in the SI release of noradrenaline. 4. Captopril (5 mumol/L) blocked the facilitatory effect of angiotensin I on noradrenaline release but did not alter that of isoprenaline. 5. Saralasin (0.1 mumol/L) reduced the facilitatory effect of angiotensin II on noradrenaline release but did not alter that of isoprenaline. 6. The findings indicate that the facilitation of noradrenaline release by isoprenaline in rat atria is not mediated by local formation of angiotensin II.

Angiotensin I↗
PubMed1989

Effect of phorbol ester and pertussis toxin on the enhancement of noradrenaline release by angiotensin II in mouse atria.

1. Mouse atria were incubated with [3H]-noradrenaline, and the outflow of radioactivity due to electrical field stimulation (5 Hz, 60 s) was used as an index of noradrenaline release. Angiotensin II (0.01 and 0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity. 2. Phorbol 12-myristate 13-acetate (0.001, 0.03, 0.1 and 1.0 microM), a protein kinase C activating phorbol ester, significantly enhanced the S-I outflow of radioactivity. When angiotensin II (0.1 microM) was present with the concentration of phorbol 12-myristate 13-acetate that was maximally effective in increasing the S-I outflow (0.1 microM), the enhancement of S-I outflow produced by angiotensin II was maintained. 3. Polymyxin B (70 microM), an inhibitor of protein kinase C, significantly inhibited the S-I outflow. Polymyxin B also inhibited the enhancement of the S-I outflow produced by angiotensin II (0.1 microM). 4. In another series of experiments mice were injected with pertussis toxin (1.5 micrograms per mouse), 4 days before their atria were removed. The effectiveness of pertussis toxin pretreatment was determined indirectly using carbachol. Carbachol caused a concentration-dependent fall in both the rate and force of beating of isolated spontaneously beating atria from mice pretreated with vehicle. This effect of carbachol was not seen with atria from mice pretreated with pertussis toxin. 5. Pertussis toxin pretreatment did not alter the enhancement of the S-I outflow of radioactivity produced by angiotensin II (0.01 and 0.1 microM). 6. These results suggest that angiotensin II receptor modulation of noradrenaline release is not mediated through either a pertussis toxin sensitive guanine nucleotide-binding protein or activation of protein kinase C.

Angiotensin II↗
PubMed1988

[Roentgen morphology of bone metastases of breast cancer as affected by antineoplastic therapy].

The changes in bone metastases from carcinoma of the breast induced by treatment have been analysed from their radiological appearances in a series of 58 patients and for an average period of 7.2 years. Indicators of regression are recalcification or re-ossification of primary osteolyses (46.8%), the development of marginal sclerosis round the defect (15.9%) and lack of progression over a period of 9 to 12 months (11.6%). Decreased sclerosis in primary osteosclerotic metastases (9.4%) may also be evidence of regression. Primary osteolytic/osteosclerotic metastases behave similar as osteolytic lesions. Recurrence or progress of tumour produces new metastases (39.6%), progressive osteolysis (26.6%), sclerosis (7.3%) and increased tumour size (15.4%).

Adult↗
PubMed1988

Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional beta-adrenoceptors and angiotensin receptors.

1. Isolated preparations of rat anococcygeus muscle were incubated with [3H]-noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as a measure of release of transmitter noradrenaline. Isometric contractile responses were also measured. 2. Angiotensin I (0.03 microM) and angiotensin II (0.03 microM) produced non-sustained contractile responses and enhanced the stimulation-induced (S-I) effluxes of radioactivity as well as the contractile responses to electrical stimulation. These effects were blocked by the angiotensin II receptor antagonist saralasin (0.03 microM), and the effect of angiotensin I, but not angiotensin II, was blocked by the angiotensin converting enzyme inhibitor captopril (0.1 microm). 3. The findings indicate that there are both pre- and postjunctional receptors for angiotensin II and that angiotensin I is converted to angiotensin II in the anococcygeus muscle preparation. 4. Isoprenaline (0.1 microM) slightly enhanced the S-I efflux of radioactivity, and produced a greater enhancement after neuronal uptake blockade with desipramine (0.03 microm) and alpha-adrenoceptor blockade with phentolamine (1 microM). 5. The facilitatory effect of isoprenaline on S-I efflux of radioactivity was abolished by propranolol (0.3 microM), but was not affected by low concentrations of saralasin (0.03 microM) or captopril (0.1 microM) which abolished the effect of angiotensin I. The findings suggest that isoprenaline acts directly on prejunctional beta-adrenoceptors to enhance S-I noradrenaline release, rather than indirectly by releasing angiotensin II from within the tissue. Higher concentrations of saralasin (0.1 microM) or captopril (5 microM) did block the facilitatory effect of isoprenaline. The significance of this finding is not clear.

Angiotensin I↗
PubMed1988

Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, beta-adrenoceptors and angiotensin II receptors.

1. In rabbit pulmonary artery and left atrial strips previously incubated with [3H]-noradrenaline, the active fragment of adrenocorticotropic hormone (ACTH 1-24, 0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity when a cocktail containing corticosterone (40 microM), cocaine (30 microM) and propranolol (4 microM) was present, but not in the absence of these drugs. In rabbit pulmonary artery a facilitatory effect of ACTH 1-24 (0.1 microM) was also observed when only cocaine (30 microM) was present. 2. ACTH 1-24 (0.1 microM) did not affect the S-I outflow of radioactivity from rat atria, rat pulmonary artery or guinea-pig pulmonary artery, either in the presence or in the absence of the cocktail containing corticosterone (40 microM), cocaine (30 microM) and propranolol (4 microM). These results suggest that the presence of facilitatory prejunctional ACTH receptors may be restricted to rabbit sympathetic nerve endings. 3. Angiotensin II (0.01 microM), but not isoprenaline (0.1 microM) or ACTH 1-24 (0.1 microM), significantly enhanced the S-I outflow of radioactivity from rabbit pulmonary artery. In the presence of phentolamine (1 microM) to block inhibitory alpha 2-adrenoceptors, the facilitatory effect of angiotensin II (0.01 microM) was significantly enhanced, and a significant facilitatory effect of isoprenaline (0.1 microM) and of ACTH 1-24 (0.1 microM) was then revealed. These results suggest that feedback inhibition of noradrenaline release, mediated through the prejunctional alpha 2-adrenoceptor mechanism, buffers increases in noradrenaline release during activation of facilitatory prejunctional receptors. 4. In rabbit pulmonary artery, two concentrations of 8-Br-cyclic AMP, (270 or 540 microM), enhanced the S-I outflow of radioactivity in the presence of phentolamine (1 microM) to a similar extent. In the presence of 8-Br-cyclic AMP (270 microM) and phentolamine, the facilitatory effects of isoprenaline (0.1 microM) and of ACTH,24 (0.1 microM) were blocked, whereas that of angiotensin II (0.01 microM) was not changed. These results suggest that both prejunctional beta-adrenoceptors and ACTH receptors enhance noradrenaline release by generating cyclic AMP. The mechanism by which angiotensin II facilitates noradrenaline release is probably independent of the cyclic AMP second messenger pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Pertussis toxin does not attenuate alpha 2-adrenoceptor mediated inhibition of noradrenaline release in mouse atria.

1. The alpha 2-adrenoceptor agonist clonidine (0.03 and 0.1 mumol/l) significantly inhibited stimulation-induced overflow of radioactivity from mouse isolated atria preincubated with [3H]-noradrenaline. This effect of clonidine was blocked by idazoxan (0.3 mumol/l) but not prazosin (0.3 mumol/l), indicating that an alpha 2-adrenoceptor was involved. 2. In some experiments mice were injected with pertussis toxin (1.5 micrograms/mouse) 4 days before their atria were removed and subsequently incubated with [3H]-noradrenaline. Alternatively, isolated atria from untreated mice were suspended in Krebs-Henseleit solution, incubated for 16 h with pertussis toxin (1.0 and 4.0 micrograms/ml) or vehicle and subsequently incubated with [3H]-noradrenaline. The effectiveness of pertussis toxin pretreatment was assessed indirectly using carbachol. Carbachol caused a dose dependent fall in both the rate and force of contraction of isolated, spontaneously beating atria from mice pretreated with vehicle in vivo or in vitro. This effect of carbachol was not seen in atria from mice pretreated with pertussis toxin in vivo or in vitro, suggesting that active toxin penetrated the myocardium. 3. Pertussis toxin pretreatment, either in vivo or in vitro did not alter the inhibitory effect of clonidine (0.03 and 0.1 mumol/l), or the facilitatory effect of the alpha-adrenoceptor antagonist phentolamine (1.0 mumol/l), on the stimulation-induced overflow of radioactivity. These results suggest that alpha 2-adrenoceptor modulation of noradrenaline release from sympathetic nerve terminals is not dependent on an inhibitory guanine-nucleotide-binding protein.

Adrenergic alpha-Agonists↗
PubMed1987

Modulation of norepinephrine release through alpha 1- and alpha 2-adrenoceptors in rat isolated kidney.

The aim of this study was to investigate alpha-adrenoceptor modulation of norepinephrine (NE) release from sympathetic nerves in rat isolated perfused kidney. After preincubation with [3H]NE, the renal nerves were stimulated. The stimulation-induced (S-I) outflow of radioactivity was used as an index of NE release. Clonidine (0.1 mumol/L) decreased the S-I outflow of radioactivity. This effect was abolished by the alpha 1-adrenoceptor antagonist idazoxan (0.1 mumol/L) but not by the alpha 2-adrenoceptor antagonist prazosin (0.1 mumol/L). Methoxamine (10 mumol/L) also had an inhibitory effect; this was abolished by prazosin (0.1 mumol/L), but not by idazoxan. Individually, these alpha-blocking drugs and the alpha 1-adrenoceptor antagonist corynanthine (0.3 mumol/L) enhanced S-I outflow of radioactivity. In the presence of indomethacin (10 mumol/L), the inhibitory effect of methoxamine was abolished but clonidine still inhibited S-I outflow of radioactivity. The facilitatory effect of prazosin was also unaltered by indomethacin. These results suggest the existence of inhibitory prejunctional alpha 1- and alpha 2-adrenoceptors in the kidney. The inhibitory effect of methoxamine seems to be mediated through prostaglandin inhibition of NE release. However, the evidence for inhibitory prejunctional alpha 1-adrenoceptors rests solely on the facilitatory effects of prazosin and corynanthine.

Adrenergic alpha-Agonists↗
PubMed1987

Modulation of noradrenaline release in vivo through prejunctional alpha-adrenoceptors.

1. Extensive in vitro studies have suggested that noradrenaline release from sympathetic nerve endings is modulated by alpha 2-adrenoceptors on the terminal varicosities, activation of which by alpha-adrenoceptor agonists or neuronally released noradrenaline leads to inhibition of transmitter release. 2. Studies in intact animals support essentially the physiological operation of this mechanism, whereas human studies have reached mixed conclusions and more information is required.

Animals↗
PubMed1987

Involvement of cyclic nucleotides in prejunctional modulation of noradrenaline release in mouse atria.

1 In mouse isolated atria previously incubated with [3H]-noradrenaline, 8-bromo-cyclic AMP (3-270 microM) produced a concentration-dependent increase in the fractional stimulation-induced outflow of radioactivity. 8-Bromo-cyclic GMP induced a lesser increase in the stimulation-induced outflow. 2 The phosphodiesterase inhibitors: M&B 22948 (90 microM); ICI 63197 (30 and 90 microM) and 3-isobutyl-1-methylxanthine (90 microM) increased the fractional stimulation-induced outflow. Together these results indicate that cyclic AMP may have a modulatory effect on noradrenaline release. 3 The inhibition of the stimulation-induced outflow produced by clonidine (0.03 microM) and its facilitation produced by phentolamine (1 microM) were unaltered in the presence of 8-bromo-cyclic AMP (90 microM). However, in the presence of 8-bromo-cyclic AMP (270 microM), the facilitatory effect of phentolamine was enhanced, but the inhibitory effect of clonidine (0.03 microM) was unaltered. In the presence of ICI 63197 (30 microM) the inhibitory effect of clonidine (0.03 microM) was unaltered, but the facilitatory effect of phentolamine (1 microM) was slightly enhanced. 4 Isoprenaline (0.003-0.1 microM) enhanced the fractional stimulation-induced outflow, an effect blocked by propranolol (0.1 microM). In the presence of 8-bromo-cyclic AMP (90 microM), the facilitatory effect of isoprenaline (0.01 microM) was blocked. In the presence of ICI 63197 (30 microM) the facilitatory effect of isoprenaline (0.003 microM) was potentiated. 5 These results suggest that whereas beta-adrenoceptor-mediated enhancement of noradrenaline release is linked to the stimulation of adenylate cyclase and enhanced formation of cyclic AMP, alpha-adrenoceptor-mediated inhibition of noradrenaline release is not linked to inhibition of adenylate cyclase activity.

8-Bromo Cyclic Adenosine Monophosphate↗