摘要:

SUMMARY1. Noradrenaline‐induced contractions of the rabbit and rat isolated aorta and guinea‐pig spleen strips were inhibited by concentrations of phenoxybenzamine which did not affect responses to calcium. This may suggest a specific action on α‐adrenoceptors. However, analysis of noradrenaline concentration‐effect curves in guinea‐pig spleen indicated that 1 μmol/1 phenoxybenzamine should have reduced the available receptor population to 6% of control, but data from radioligand binding experiments on the same tissues using [3H]‐prazosin indicated a reduction of the receptor population to only 82% of control. The reduced responsiveness observed in the organ bath study after phenoxybenzamine pretreatment, whilst not apparently related to effects on voltage‐dependent calcium channels, could be due to the actions of phenoxybenzamine on other (non‐receptor) processes such as receptor‐operated calcium channels.2. Maximal contractile responses to histamine in rabbit isolated aorta but not those in guinea‐pig isolated ileal preparations, were depressed by concentrations of phenoxybenzamine which depressed responses to calcium. Phenoxybenzamine produced parallel rightward shifts of curves to carbachol in guinea‐pig ileal preparations but only depressed maximal responses to the agonist in higher concentrations which reduced responses to calcium.3. On the basis of the results obtained with calcium it is possible that the effects of phenoxybenzamine on receptor‐mediated responses could be produced through the actions of this antagonist at less specific sites such as voltage‐dependent calcium channels for histamine in rabbit aorta and carbachol in guinea‐pig ileum. For α‐receptor mediated responses in aortic and splenic strip preparations and for histamine‐mediated responses in guinea‐pig ileum, the actions of phenoxybenzamine may reflect an interaction of the antagonist wit

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00895.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. Isometric tension was recorded from strips of bovine tracheal smooth muscle in which the tone had been artificially raised by agonist drugs such as histamine and carbachol.2. Application of exogenous acetylcholine produced a biphasic response consisting of an initial contraction followed by a more prolonged relaxation before tone was restored to normal.3. Atropine blocked both components of the biphasic response to exogenous acetylcholine.4. Tetrodotoxin blocked neither phase of the response to exogenous acetylcholine even though a similar biphasic response to electrical stimulation was severely disrupted.5. Application of exogenous substance P produced a biphasic response of similar magnitude and form to that produced by acetylcholine.6. Application of exogenous histamine (tone raised by carbachol) also produced a biphasic response although higher concentrations were required to produce a relaxation of equal magnitude to that produced by acetylcholine.7. It is concluded that the inhibitory component of the biphasic response to exogenous acetylcholine occurs as a non‐specific sequel to contractio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00896.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. Cimetidine produced a dose‐dependent and reversible inhibition of contractions of the nictitating membrane elicited through stimulation of the preganglionic nerve supplying the superior cervical ganglion in the anaesthetized cat. Postganglionic nerve stimulation resulted in only a slight and variable inhibition of the contractions. Both hexamethonium and cimetidine also produced a dose‐dependent and reversible fall in arterial blood pressure.2. The ganglion blocking activity of cimetidine was much weaker than that of hexamethonium; the ED50ratio (cimetidine:hexamethonium) calculated from the cumulative log dose‐response curves for the two drugs was 64.3. The possible mechanism(s) of ganglion blockade produced by cimetidine is discussed including a possible action at nicotinic receptors, either directly or indirectly (via its anticholinesterase activity), and ion channel blockade.4. The clinical implications of cimetidine‐induced ganglionic blockade are also discussed, especially with respect to sexual impotence associated with the use of cim

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00897.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The inhibitory effect of morphine, nalorphine, oxymorphone, naloxone, naltrexone,N‐methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo‐methadone, dextro‐methadone, pethidine, leu‐enkephalin and U‐50 488 on the acetylcholine (ACh)‐induced contraction of the toad rectus was investigated.2. The dose‐response curves obtained in the absence and presence of increasing concentrations (0.1–3.2 or 10–320 μmol/l) of each opioid were subjected to three types of inhibition model discrimination, namely competitive, noncompetitive and uncompetitive.3. The results show that the opioids, except morphine, nalorphine and levorphanol, inhibit the ACh‐induced contraction by multiple modes of action. Except for the morphinans, the opioids inhibit competitively indicating that they are able to compete with ACh for cholinergic receptors at the nicotinic site.4. The opioids also inhibit noncompetitively (except oxymorphone andN‐methylnaloxone) and uncompetitively (except oxymorphone) indicating the possible existence of separate opioid binding sites and the combination of the opioids with the ACh receptor complex, respectively.5. The effect of morphine and levorphanol on the ACh‐induced contraction varies with the concentration of the two opioids. At concentrations below 80 μmol/l both opioids tend to inhibit the contraction while at concentrations of 80 μmol/l and above there is no apparent effect. Nalorphine has no effect on the contraction at the concentrations (10–320 μmol/l) employed in the study.6. An apparent structure‐activity relationship between the phenanthrenes and the various binding sites is noticeable; so also is the difference in the activity between the dextro and levo‐isomers of levorphanol and levallorphan indicating that the re

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00898.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. In order to investigate a possible relationship beween sympatho‐adrenal neuronal activity and the endocrine changes during the menstrual cycle, free and sulphate‐conjugated plasma catecholamines and oestradiol were measured under carefully controlled conditions in 26 normal menstruating women.2. Plasma oestradiol levels were generally higher during the luteal compared with the follicular phase which corresponded to the self‐reported day of the cycle.3. Free plasma noradrenaline concentration was higher during the luteal phase (P= 0.02) and was positively correlated with plasma oestradiol concentration (r= 0.40,P= 0.023). These relationships were not present for plasma adrenaline.4. It is conceivable that the higher luteal phase noradrenaline is causally related to the higher oestradiol levels, leading to incomplete inactivation by reducing tissue uptake or competitive inhibition of catechol‐O‐methyl transferase.5. As sulphated noradrenaline was not significantly different between the follicular and luteal phases, competitive inhibition of phenolsulphotransferase by oestradiol was considered

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00899.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. To determine whether vascular resistance was altered in diabetes, the vascular resistance in both the peripheral arterial bed and the circumflex coronary artery was compared in six normal and five diabetic adult sheep, under pentobarbitone anaesthesia. Diabetes induced by alloxan significantly increased blood glucose (15.6mmol/l, s.e.m. = 2.8, vs 5.5 mmol/l, s.e.m. =0.6;P>0.001) compared with controls.2. Systolic blood pressure was lower in diabetics (92 mmHg, s.e.m. = 12, vs 123 mmHg, s.e.m. =5;P0.05).3. Basal peripheral resistance was lower in diabetics than controls (36.0 mmHg. min/1, s.e.m. = 7.9, vs 42.3 mmHg.min/1, s.e.m. =2.8), but not significantly so.4. Methoxamine markedly increased peripheral vascular resistance in both groups, but did not change coronary vascular resistance, due to autoregulation. The dose‐response curves of peripheral or coronary arteries to methoxamine showed no significant difference between diabetic and control sheep. Dose‐response curves for isoprenaline and noradrenaline infusion suggested there may be altered β‐receptor sensitivity in diabetes.5. In conclusion, there are marked differences in the vascular beds of diabetic and normal sheep under basal conditions. In contrast to previous studies, α‐adrenoceptors are not different in diabetics, but further studies in unanaesthetized animals are indicated, as β‐receptor sensitivity may be altered

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00900.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. AR‐C 239, a new α‐adrenoceptor blocking drug, appears to act selectively on α1sites in rats. At peripheral sites, this drug did not change the tachycardia induced by spinal sympathetic outflow stimulation in pithed rats, and did not antagonize the inhibitory effects of clonidine on this preparation. In addition, AR‐C 239 showed predominant α1‐adrenoceptor blocking properties in the bisected rat vas deferens preparation. AR‐C 239 did not prevent or reverse the centrally mediated hypotensive and bradycardic actions induced by clonidine, in intact animals.2. In conclusion, AR‐C 239 seems to be a very useful tool for the characterization of peripheral and central α1‐adrenoceptors, in th

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00901.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The coronary vasodilatory effect of stable adenosine analogues is mediated by adenosine A2receptors.2. These coronary receptors differ from A2receptors found in other tissues.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00902.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. In order to assess the effects of Bay‐K‐8644 on electrical activities of young embryonic chick hearts in which the rising phase of the action potential (AP) depends on tetrodotoxin‐insensitive slow Na+currents, slow AP were recorded in spontaneously beating 3‐day‐old embryonic chick hearts.2. Bay‐K‐8644(10‐6mol/l) caused increases in the maximum rate of rise, amplitude, and duration of the slow AP; there was a slow increase in the spontaneous firing rate.3. Thus, Bay‐K‐8644 stimulates Na+influx through TTX‐inse

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00903.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARY1. The characteristics of the inhibition of electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by the antimalarial agents mefloquine, chloroquine, amodiaquine and amopyroquine were determined.2. The antimalarials were found to be non‐competitive inhibitors of both AChE and BChE. In both enzyme systems, inhibitory potencies were in the order amodiaquine>amopyroquine>chloroquine>mefloquine.3. The low inhibitory potency of mefloquine may account in part for the appearance of gastrointestinal and central nervous system disturbances only at high doses of the dru

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1985.tb00904.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY