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PubMed1984

Comparison of three hypotensive anaesthetic methods for middle ear microsurgery.

Three hypotensive anaesthetic methods were compared in 123 patients undergoing middle ear microsurgery. Hypotension was induced with halothane (1 vol.%), nitroprusside (4.4 micrograms/kg/min) or the combination of halothane (0.5 vol.%) and nitroprusside (1.2 micrograms/kg/min). The compensatory rise in the heart rate was controlled with a beta-adrenergic receptor blocking agent, practolol, the mean need for which was 0.03 mg/kg in the halothane group and 0.1 mg/kg in the other groups. The mean duration of the hypotensive period ranged from 79 to 107 min in the groups. During the hypotension, the average mean arterial pressure ranged from 55 to 60 mmHg (7.33 to 8.00 kPa) and the mean heart rate from 67 to 79 beats/min in the groups. The PaO2 value in the nitroprusside and halothane + nitroprusside groups, but not in the halothane group, decreased statistically and in some cases clinically significantly. The only peroperative side effects were ECG changes (mostly junctional rhythm), the incidence of which ranged from 16 to 24% in the groups. The mean values for the degree of haemostasis rated by the otologist on a visual analogue scale between poor (0 mm) and excellent (100 mm) were 90, 73 and 89 mm in the halothane, nitroprusside and halothane + nitroprusside groups, respectively. Recovery in the halothane group was statistically highly significantly longer than in the other groups. No rebound hypertension occurred in any of the groups after discontinuation of the hypotension. The most common side effect was nausea + vomiting, the incidence of which ranged from 15 to 26% in the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1988

Characterization of dopamine and beta-adrenergic receptors linked to cyclic AMP formation in intact cells of the clone D384 derived from a human astrocytoma.

3,4-Dihydroxyphenylethylamine (dopamine) and beta-adrenergic receptor agonists and antagonists were assessed for their effects on cyclic AMP accumulation in human astrocytoma derived clone D384 cells. Dopamine, SKF 38393, and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene increased cyclic AMP content with Ka values of 2.0, 0.2, and 1.6 microM. The D1-selective antagonists SCH 23390 (Ki, 1.2 nM) and SKF 83566 (Ki, 0.8 nM) were over 5,000-fold more potent than the D2-selective antagonist domperidone (Ki, 6.7 microM) at inhibiting dopamine stimulation of cyclic AMP formation. SCH 23388 (Ki, 560 nM; the S-enantiomer of SCH 23390) was 400-fold less potent than SCH 23390. Isoprenaline, adrenaline, salbutamol, and noradrenaline increased cyclic AMP content with Ka values of 0.13, 0.12, 0.22, and 7.60 microM. The beta 2-selective antagonist ICI 118,551 (Ki,0.8 nM) was almost 8,000-fold more potent than the beta 1-selective antagonist practolol (Ki, 5.9 microM) at inhibiting isoprenaline stimulated cyclic AMP accumulation. These results demonstrate that D384 cells express D1-dopamine and beta 2-adrenergic receptors linked to adenylate cyclase. Furthermore, the dopamine receptor expressed by D384 cells exhibits a pharmacological profile typical of a mammalian striatal D1-receptor and therefore the use of this clone represents another approach to studying central D1-receptors.

1-Methyl-3-isobutylxanthine↗

PubMed1973

Further studies regarding the structure activity relationships of beta-adrenoceptor antagonists.

1. The ortho (M66,527) and para (M66,368) analogues of 1-t-butylamino-3-(methoxyphenoxy)-2-propanol and para substituted tertiary butylphenoxy-1-N-isopropylamine-3 propanol-2 oxalate acid (L8429) were tested in dogs for their beta-adrenoceptor blocking activity.2. M66,527, which contains a methoxy group in the ortho position of the benzene ring, was found to be comparable to propranolol in blocking cardiac and peripheral vascular responses to isoprenaline. Like propranolol, M66,527 was more potent on peripheral receptors.3. Transference of the methoxy group to the para position (M66,368) reduced the overall potency; however, this compound was found to be relatively cardioselective in that it was 2 to 3.6 times more active in blocking cardiac responses to isoprenaline.4. The cardioselective properties of the short chain para methoxy substituent were less than those reported for compounds with longer para substitutions (i.e. practolol, para oxprenolol and para alprenolol).5. L8429, with a tertiary butyl group in the para position, was a weak beta-adrenoceptor antagonist without cardioselective properties. A longer, less bulky n-butyl group may provide for a more potent and selective antagonist.6. The results support the view that the size and site of the substituent on the benzene ring may be of importance in determining the cardioselective potency of beta-adrenoceptor antagonists.

Adrenergic beta-Antagonists↗

PubMed1974

Can the actions of adrenoceptor agonists and antagonists on pentagastrin-induced gastric secretion be due to their effects of histamine formation?

1 The effects of some adrenoceptor agonists and antagonists which have been reported to affect histamine formation in leucocytes (Assem & Feigenbaum, 1972) have been investigated on gastric secretion in conscious dogs with Heidenhain pouches.2 Submaximal secretion in response to pentagastrin was enhanced by propranolol (0.1-1.0 mg/kg i.v.) and phenylephrine (1.0 mug kg(-1) min(-1) i.v. for 20 min), which increase histamine formation, and was decreased by phentolamine (2 mg/kg i.v.) and isoprenaline (0.05-0.2 mug kg(-1) min(-1) i.v. for 30 min), which decrease histamine formation. Practolol (2 mg/kg i.v.), which has no effect on histamine formation, had no effect on secretion.3 Acid secretion in response to histamine was either unaffected or affected in the opposite direction by these drugs.4 The effects of the drugs on pentagastrin-induced secretion were not secondary to changes in mucosal blood flow (radioactive aniline clearance).5 The results are consistent with the hypothesis that acid secretion in response to pentagastrin involves the formation of endogenous histamine.

Animals↗

PubMed1977

Differentiation of metabolic adrenoceptors.

1 Cardiovascular and metabolic responses to intravenous infusion of isoprenaline were measured in fasted, anaesthetized cats. 2 Isoprenaline (0.2 mug kg-1 min-1 for 15 min) decreased diastolic blood pressure and increased heart rate, blood glucose, blood lactate and plasma free fatty acids. 3 Oxprenolol (0.5 mg/kg) antagonized all cardiovascular and metabolic effects of isoprenaline non-selectively. 4 Para-oxprenolol (0.25 mg/kg) and practolol (4 mg/kg) antagonized the effects of isoprenaline on heart rate and free fatty acids selectively. 5 H 35/25 ((I-(4-methylphenyl)-2-isopropyl aminopropanol) hydrochloride, 3 mg/kg) antagonized the effects of isoprenaline on blood pressure, glucose and lactate selectively. 6 It is concluded that metabolic adrenoceptors are differentiated into subtypes similar to those mediating cardiostimulation and vasodilatation.

Adrenergic beta-Antagonists↗

PubMed1979

alpha And beta-adrenoceptors in the detrusor muscle and bladder base of the pig and beta-adrenoceptors in the detrusor muscle of man.

1 The presence and type of adrenoceptors in the smooth muscle of the pig and human urinary bladder was assessed on the basis of the relative potency of alpha- and beta-adrenoceptor agonists and antagonists.2 In isolated, carbachol-contracted bladder strips from the pig detrusor muscle the relaxing potency of isoprenaline was four times that of salbutamol and ritodrine and thirty times that of noradrenaline.3 Propranolol caused a parallel shift to the right of the noradrenaline dose-response curve which was not changed by phentolamine.4 Propranolol and butoxamine showed, in contrast to practolol, a dose-dependent antagonism of the response to isoprenaline. A pA(2) value of 9.2 +/- 0.2 and 6.8 +/- 0.2 (mean +/- s.e. mean) for the first two antagonists was calculated.5 In the bladder base of the pig, propranolol caused a parallel shift to the right and phentolamine a shift to the left of the dose-response curve to noradrenaline.6 In the human detrusor muscle the potency and maximum effect of isoprenaline and salbutamol were less than those in the pig detrusor muscle. The potency of isoprenaline was sixty times that of salbutamol.7 Whereas a parallel shift to the right of the dose-response curve to isoprenaline was obtained with propranolol, no antagonism was obtained with butoxamine or practolol.8 The results are interpreted as indicating the presence of beta(2)-adrenoceptors in the detrusor muscle of the pig and beta-adrenoceptors with neither beta(1)- nor beta(2)-characteristics in the detrusor muscle of man. An indication of the presence of alpha-adrenoceptors in the bladder base but not in the detrusor muscle of the pig was obtained.

Adult↗

PubMed1979

An analysis of the negative inotropic action of somatostatin.

1 Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea-pigs.2 SS was completely inactive in rat and rabbit auricles but exerted a dose-dependent, negative inotropic effect in guinea-pig auricles in concentrations between 1.5 x 10(-8) to 1.2 x 10(-6) M.3 The negative inotropic effect of SS (6.0 x 10(-8) and 3.0 x 10(-7) M) was not inhibited by a mixture of antagonists containing practolol (7.9 x 10(-6) M), phentolamine (3.5 x 10(-7) M), methysergide (2.8 x 10(-7) M), diphenhydramine (3.9 x 10(-5) M), cimetidine (4.0 x 10(-5) M) atropine (3.4 x 10(-7) M) and indomethacin (1.4 x 10(-5) M).4 The negative inotropic effect of SS was greatly potentiated by reduction in the Ca(2+) concentration of the medium from 5.0 to 1.25 mM.5 On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea-pig auricles.6 SS (6.0 x 10(-8) and 6.0 x 10(-7) M) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea-pig but not in rat auricles.7 The inhibitory action of SS against NT was independent of its negative inotropic action.8 These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea-pig atria. The interaction between SS and its receptor may cause a decreased Ca(2+) diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed.

Acetylcholine↗

PubMed1980

alpha-Sympathomimetic amines and calcium-mediated action potentials in guinea-pig ventricular muscle.

1 The ability of amines, having alpha- or alpha- and beta-adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea-pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via alpha-adrenoceptors. 2 In preparations in which fast sodium channels were inactivated by K+-rich medium (22 mM) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10(-4) to 3 X 10(-4) M) and synephrine (3 X 10(-4) M). 3 The restorative effective effects of both phenylephrine and synephrine were unaffected by phentolamine (10(-5) M) but were readily abolished by practolol (10(-5) M) or sotalol (10(-5) M). 4 Methoxamine induced a dose-dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10(-4) M. However, at the same concentration, the amine did not induce slow electrical responses in potassium-depolarized preparations. 5 It is concluded that the induction of slow responses by phenylephrine and synephrine is due to beta-adrenoceptor stimulation, and that the increase in cardiac contractility caused by alpha-adrenoceptor stimulation does not involve an increase in slow inward calcium current.

Action Potentials↗

PubMed1981

Development of a severe model of early coronary artery ligation-induced dysrhythmias in the anaesthetized rat.

1. The potential use of catecholamines to increase the severity of dysrhythmias evoked by coronary artery ligation in the anaesthetized rat was investigated. Drugs were given intravenously prior to ligation. 2 Pressor doses of adrenaline (5 microgram/kg) noradrenaline (1 microgram/kg) phenylephrine (5-10 microgram/kg), and angiotensin (0.25 microgram/kg) conferred protection against the development of dysrhythmias. 3 Atropine (1 mg/kg) increased mortality from ventricular fibrilloflutter (VF) and abolished the protective effects of phenylephrine (10 micrograms/kg). 4 Administration of isoprenaline (10 microgram/kg) significantly increased the incidence of and the mortality from VF. 5 The order of antidysrhythmic drug potency of Org 6001 (1-10 mg/kg), disopyramide (2-10 mg/kg) and practolol (2-10 mg/kg) was similar in both the standard (without isoprenaline) and modified (with isoprenaline) models. 6 Use of the modified method for antidysrhythmic screening purpose allows demonstration of statistically meaningful results with the use of relatively few animals. 7 Comparison of the pattern of VF in the rat heart induced by various means suggests that the diagnosis of ventricular fibrillation can be made with more confidence in the modified method compared to the standard method.

Androstanols↗

PubMed1983

Propranolol-induced airway hyperreactivity in guinea-pigs.

In anaesthetized, spontaneously breathing guinea-pigs, enhanced bronchoconstrictor responses (increases RL) to histamine were measured following intravenous injection of practolol, (+/-)-propranolol, (+)- and (-)-propranolol. Propranolol enhanced not only histamine- but 5-hydroxytryptamine (5-HT)-induced bronchoconstrictions and its effects lasted up to 2 h. This increased airway sensitivity was not due to beta-adrenoceptor blockade because: (a) similar effects were produced by racemic propranolol and its two isomers (+)- and (-)-propranolol and (b) whilst equal doses of (+/-)- and (+)-propranolol produced the same potentiation of histamine bronchoconstriction, only (+/-)-propranolol also caused a measurable beta-adrenoceptor blockade in the airways. The enhanced histamine- and 5-HT-induced bronchoconstrictions were antagonized by the leukotriene antagonist FPL 55712 and by the lipoxygenase/cyclo-oxygenase inhibitor BW755c. The results demonstrate that endogenously released leukotrienes can produce not only a direct bronchospasm but may enhance the effects of other bronchoconstrictor agents. The relevance of this leukotriene-mediated hyperreactivity to the non-specific airway hyperreactivity seen in asthmatics is discussed.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1986

The beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat.

The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. All the compounds studied caused a concentration-dependent increase in atrial frequency and relaxation of the uterus. The atrial response to pindolol was competitively inhibited by the beta 1-selective blocker pafenolol (10(-7) M), while the beta 2-selective blocker ICI 118551 (10(-8) M) was without effect. Pafenolol (10(-7) M) was also shown to inhibit the atrial frequency effect of alprenolol and oxprenolol. In the uterus, ICI 118551 (3 X 10(-9) M, 3 X 10(-8) M, 3 X 10(-7) M) blocked the pindolol effect with a pKB of 9.28. In addition, ICI 118551 (10(-8) M) competitively inhibited the relaxation of the uterus induced by alprenolol and oxprenolol. For alprenolol (right atrium and uterus), oxprenolol (right atrium), and pindolol (right atrium), the concentrations needed for half-maximal response were significantly greater than those required for occupation of half the receptors. This dissociation was most pronounced for pindolol in the right atrium. In this tissue, 80-85% of the beta 1-adrenoceptors had to be occupied by pindolol to initiate a tissue response corresponding to 50% of the maximal effect generated by the compound. The intrinsic activities of alprenolol, oxprenolol and pindolol (expressed as % of the maximal tissue response to isoprenaline) were significantly higher in the uterus than in the right atrium. The intrinsic activity of the compounds varied between individual preparations and, particularly in the uterus, correlated with the sensitivity of the tissue to beta-adrenoceptor stimulation by isoprenaline. 5 Calculation ofefficacy, relative to isoprenaline, of the partial beta-agonists revealed a beta 2-adrenoceptor selectivity for alprenolol (2.0), oxprenolol (1.4) and pindolol (3.0). 6 It is concluded that weak partial agonists such as alprenolol, oxprenolol and pindolol possess complex beta 1- and beta 2-adrenoceptor stimulatory properties in relation to beta-adrenoceptor occupancy and tissue sensitivity to beta-adrenoceptor stimulation.

Adrenergic beta-Agonists↗

PubMed1988

The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle. It is also suggested that CTX activates cardiac muscle Na channels by modifying the voltage-dependence of channel activation to increase Na inward currents, thus producing cardiotonic actions.

Action Potentials↗

PubMed1990

Subclassification of beta-adrenoceptors responsible for steroidogenesis in primary cultures of bovine adrenocortical zona fasciculata/reticularis cells.

1. Forty eight hour primary cultures of purified bovine adrenocortical zona fasciculata/reticularis cells secreted hydrocortisone in response to stimulation with beta-adrenoceptor agonists. The observed order of potency was isoprenaline greater than noradrenaline greater than dobutamine greater than salbutamol greater than BRL37344. 2. Salbutamol acted as a partial agonist on these cells hence suggesting the presence of a beta 1-adrenoceptor. 3. Schild analysis of the hydrocortisone response to isoprenaline showed that the selective beta 1-antagonist practolol and the selective beta 2-antagonist ICI118,551 gave pA2 values of 6.85 and 7.17, respectively. These values were in close agreement with corresponding pA2 values previously obtained for the beta 1-adrenoceptor. 4. We conclude that beta 1-adrenoceptors are responsible for mediating catecholamine-stimulated hydrocortisone secretion from primary cultures of bovine zona fasciculata/reticularis cells.

Adrenergic beta-Agonists↗

PubMed1977

Effect of propranolol and related drugs on transmembraneous pH differences in liposomes.

Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane.

4-Aminobenzoic Acid↗

PubMed1982

Pharmacological isolation of a single beta-adrenoceptor subtype makes Schild plots which have slopes of 1 possible for selective beta-adrenoceptor antagonists in carbachol-contracted guinea-pig trachea.

The effects of selective beta-adrenoceptor agonists and antagonists on isometric relaxation of carbachol-contracted, guinea-pig isolated trachea were studied. An attempt was made to pharmacologically isolate the beta 1- and beta 2-adrenoceptors by use of appropriate selective agonists and antagonists. The slopes of the Schild plots for butoxamine vs noradrenaline and terbutaline as well as for practolol vs terbutaline did not differ significantly from 1, the predicted value for a competitive antagonist acting at a single receptor type. These data differ from a previous report suggesting that slopes of less than 1 are characteristic for selective beta-adrenoceptor antagonists in carbachol-contracted guinea-pig trachea. They support the hypothesis that the slopes in this preparation are due to interaction of the agonist with both beta 1- and beta 2-adrenoceptors rather than the state of contraction of the trachea.

Adrenergic beta-Antagonists↗

PubMed1984

Chronic treatment with electroconvulsive shock prevents the salbutamol-induced hypoactivity in rats.

Several lines of evidence (binding studies, reduced responsiveness of brain adenylate cyclase to noradrenergic stimulation) indicate that chronic treatment with electroconvulsive shock (ECS) induces down-regulation of central beta-adrenoceptors. The effect of acute and chronic (10 days) treatment with ECS on salbutamol-induced suppression of exploratory activity in rats has been examined. This effect was prevented by chronic but not by acute treatment with ECS. Chronic treatment with ECS did not affect exploratory activity. The salbutamol-induced hypoactivity is mediated through central beta-adrenoceptors (antagonistic effect of (-)-propranolol but not (+)-propranolol or practolol), so the results may be regarded as functional evidence at the behavioral level for the down-regulation of beta-adrenoceptors produced by chronic treatment with ECS.

Albuterol↗

PubMed1975

Drinking behaviour in the cat induced by renin, angiotensin I, II and isoprenaline.

1. Angiotensin I, II and hog renin, infused into the lateral cerebral ventricles (I.C.V.) of water replete cats, each induced water drinking behaviour. 2. Intravenous infusion of high doses of angiotensin I or II also elicited a drinking response. The dipsogenic effect of I.V. renin was not marked. 3. Drinking in response to I.C.V. angiotensin II was abolished after autonomic ganglion blockade with I.V. hexamethonium or pempidine and was significantly reduced after I.V. atropine methonitrate. 4. The dipsogenic response to I.C.V. angiotensin II was unaffected by either peripheral adrenergic neurone blockade with I.V. bethanidine, alpha-adrenoceptor blockade with phentolamine or beta-adrenoceptor blockade with sotalol. 5. Atropine, atropine methonitrate, hexamethonium and pempidine given I.C.V did not inhibit the diposgenic response to I.C.V. angiotensin II. 6. Bethanidine I.C.V. produced a dose related reduction in the dipsogenic response to I.C.V. angiotensin II. 7. The alpha-adrenoceptor blocking agents tolazoline and phenoxybenzamine given I.C.V did not affect angiotensin induced drinking but the response was regularly inhibited by phentolamine I.C.V. 8. The beta-adrenoceptor blocking agents propranolol and practolol given I.C.V. each inhibited angiotensin induced drinking. The L-isomer of propranolol was a more effective blocker than the D-isomer. 9. Isoprenaline given I.C.V induced drinking in ten of sixteen cats. Subcutaneous administration of isoprenaline also elicited drinking but the onset of the response was delayed and the amount consumed slightly less than after I.C.V infusion.

Angiotensin II↗

PubMed1975

Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts.

1. The effects of two positively charged local anaesthetic amines, tetracaine and propranolol, on cation permeability were studied in resealed human red cell ghosts prepared from metabolically depleted erythrocytes. 2. The K permeability was reduced by tetracaine but increased by propranolol. The effect of tetracaine was independent of extracellular Ca concentration but was raised to 2-5 x 10(-7) M. The effect of propranolol, which was enhanced when the external Ca concentration was raised, could be completely inhibited by lowering the internal free Ca to less than 10(-7) M. 3. Propranolol, but not tetracaine, increased the intracellular Ca ion concentration by releasing up to 20% of the membrane-bound Ca to the cell interior. This increase in intracellular Ca was sufficient to mediate the observed change in K permeability. 4. Tetracaine and propranolol reduced the Ca binding capacity of the ghost membrane by about 20 and 40% respectively. The Ca permeability was increased by propranolol and was slightly reduced by tetracaine. 5. In high concentrations (2-7 mM) propranolol by itself moderately increased K and Na permeability, but supressed completely the Ca-induced increase in K permeability. Tetracaine in concentrations up to 4 mM enhanced the Ca-induced increase in K permeability. Higher concentrations of the drug caused lysis of the cells. 6. Maximally effective concentrations of tetracaine and propranolol inhibited the ATP-dependent Ca outward transport by 30 and 70% respectively. 7. The effects of tetracaine on K permeability were shared by the local anaesthetics prilocaine and lidocaine, those of propranolol were shared by practolol, a beta-adrenergic antagonist and tetraethylammonium, a ganglionic blocking agent. 8. It is suggested that the differences in the effects of tetracaine and propranolol on cation permeability reflect qualitatively different interactions of the two drugs with Ca binding sites on the inner surface of the membrane.

Adenosine Triphosphate↗