Concentrations Of Iso Research Articles

Beta-adrenergic and cholinergic modulation of the inwardly rectifying K+ current in guinea-pig ventricular myocytes.

1. Whole-cell patch-clamp technique was used to study the beta-adrenergic and cholinergic regulation of the inwardly rectifying K+ conductance (gK1) in isolated guinea-pig ventricular myocytes. 2. In Cl(-)-free solutions or in the presence of 9-anthracenecarboxylic acid or Co2+, bath-applied isoprenaline (Iso) partially inhibited the steady-state whole-cell conductance (gss) calculated from the steady-state current (Iss)-voltage (Iss-V) curve at membrane voltages (Vm) negative to the equilibrium potential for potassium (EK). Iss was also inhibited at Vm positive to EK when the extracellular [K+] was 20 mM. The Iso-sensitive component of gss exhibited the characteristics of the inwardly rectifying K+ conductance (gK1). 3. The Iso-induced inhibition of gK1 was reversible, concentration dependent, blocked by propranolol, mimicked by both forskolin and dibutyryl cAMP, and prevented by including a cAMP-dependent protein kinase (PKA) inhibitor in the pipette solution. These findings suggest that PKA mediates the Iso-induced inhibition of gK1. 4. The apparent dissociation constant (KD) for the concentration dependence of Iso-induced inhibition was 0.035 microM and the Hill coefficient was approximately 1.0. A maximal Iso concentration (1 microM) inhibited gK1 by 40 +/- 4.1% (mean +/- S.E.M.; n = 13). 5. Bath application of acetylcholine (ACh, 0.1 microM or more) antagonized the Iso-induced (1 microM) inhibition of gK1; [ACh] > 1.0 microM antagonized 88 +/- 2.1% (n = 10) of the inhibition. ACh increased the KD for Iso to inhibit Iso-sensitive gK1 and also reduced the maximal Iso-induced inhibition. 6. ACh-induced antagonism could be abolished by pre-incubating myocytes with pertussis toxin (PTX), suggesting that a muscarinic receptor-coupled, PTX-sensitive G protein, Gi, is involved. 7. ACh (10 microM) also antagonized approximately 70% of the dibutyryl cyclic AMP (1 mM)-induced inhibition of gK1 (n = 3), suggesting that the ACh-induced antagonism involves more than simply inhibiting the Iso-mediated activation of adenylyl cyclase via the activated Gi. 8. Intracellularly applied okadaic acid (OkA, 1 microM) did not alter gK1 (control = 134 +/- 5.1 nS vs. OkA = 136 +/- 6.1 nS), but the Iso-induced decrease in gK1 was less (P < 0.001) with OkA present (42.1 +/- 2.4 nS, n = 5) than when absent (54.0 +/- 2.2 nS, n = 10). However, ACh (10 microM) failed to antagonize Iso-induced inhibition with OkA present, suggesting involvement of a protein phosphatase.

Beta 2-adrenoceptor activation augments acetylcholine release from tracheal parasympathetic nerves

We determined the effects of isoproterenol (Iso) on parasympathetic neurotransmission in isolated equine trachealis strips by comparing the effects of Iso on the contractile response to electrical field stimulation (EFS) and acetylcholine (ACh), as well as by measuring EFS-induced ACh release. The interaction of Iso with muscarinic receptors and endogenous nitric oxide was also investigated. ACh release was measured by high-performance liquid chromatography with electrochemical detection. Iso (10(-7) M or greater) caused significantly more inhibition of EFS- than of ACh-induced contraction, an observation usually interpreted as evidence of prejunctional inhibition of ACh release. However, the latter conclusion was not supported by measurement of ACh release. Iso concentration dependently augmented ACh release, which was reversed by the beta 2-adrenoceptor antagonist ICI-118,551 but not by the beta 1-adrenoceptor antagonist CGP-20,712A. Our results indicate that activation of beta 2-adrenoceptors augments ACh release. Moreover, the comparison of inhibitory effects on EFS- and ACh-induced contraction does not provide correct information about the prejunctional actions of beta-agonists. ACh release was increased more by atropine (10(-7) M) than by Iso (10(-6) M), indicating the predominance of prejunctional inhibitory muscarinic autoreceptors over excitatory beta 2-adrenoceptors. Additionally, we found that inhibition of nitric oxide synthase by NG-nitro-L-arginine did not affect either the cholinergic contractile response or ACh release in both the absence and presence of Iso.

Altered beta-adrenergic and muscarinic response of CFTR Cl- current in dialyzed cardiac myocytes.

Autonomic regulation of the cardiac cystic fibrosis transmembrane conductance regulator (CFTR) Cl- current was studied in isolated guinea pig ventricular myocytes using various configurations of the whole cell patch-clamp technique. When currents were recorded using the conventional patch-clamp technique, it was possible to continue to activate the Cl- current on repeated exposure to isoproterenol (Iso) for up to 60 min after initiating dialysis. However, there was significant rundown of the magnitude of the Cl- current response to the maximally stimulating concentrations of Iso. In addition, the concentration of Iso that produced half-maximal activation of the Cl- current (K1/2) increased with time. Conversely, the K1/2 for acetylcholine inhibition of the Iso-activated current decreased with time. When currents were recorded using the perforated patch-clamp technique, the sensitivity to both beta-adrenergic- and muscarinic-receptor stimulation was stable. Immediately after initiation of dialysis with the conventional patch-clamp technique, the sensitivity to Iso was nearly identical to that determined using the perforated patch-clamp technique. However, the initial sensitivity to muscarinic-receptor activation was significantly greater. These results indicate that cell dialysis associated with conventional patch-clamp techniques not only results in a time-dependent rundown of current amplitude, but it also significantly alters the concentration dependence of beta-adrenergic and muscarinic-receptor regulation of ion channel function.

Beta-Adrenergic stimulation of skeletal muscle metabolism in relation to weight reduction in obese men

In a companion study [Blaak, E.E., M.A. van Baak, G.J. Kemerink, M.T.W. Pakbiers, G.A.K. Heidendal, and W.H.M. Saris. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E306-E315, 1994.], we found that during infusion of the nonselective beta-agonist isoprenaline (Iso), obese males had a lowered Iso-induced rise in arterial glycerol and nonesterified fatty acids (NEFA) and a lowered muscle NEFA oxidation. The present study was intended to investigate whether a period of weight reduction would alter this impaired fat utilization in obese males. Before and after a 5-wk diet intervention (very low calorie diet) whole body energy expenditure was determined during rest and during intravenous infusion of increasing doses of Iso. In addition, forearm muscle metabolism was investigated with Iso infusion with and without simultaneous infusion of the beta 1-blocker atenolol (AT) by measuring skeletal muscle blood flow and arteriovenous concentration differences of various metabolites across muscle. The Iso-induced whole body thermogenesis tended to increase as a result of weight loss when this response was related to the plasma Iso concentration (P = 0.09), whereas both before and after diet there were no changes in the respiratory exchange ratio during Iso infusion. The increases in arterial NEFA and glycerol concentrations as a result of Iso infusion were not significantly different before and after weight reduction. In addition, muscle NEFA uptake did not change as a result of Iso or Iso plus AT infusion both before and after diet, whereas muscle glucose uptake and lactate release tended to be more pronounced after weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of isoprenaline on Ca2+ channel current in single smooth muscle cells isolated from taenia of the guinea-pig caecum.

1. The effects of isoprenaline (Iso) on Ca2+ channel current in enzymatically isolated single cells of the guinea-pig taenia caeci were examined using the standard whole-cell voltage-clamp method. 2. Iso potentiated the voltage-dependent Ca2+ current; the threshold and maximally effective concentration of Iso to increase Ca2+ current were 3-10 nM and 1-3 microM, respectively. The average increase in Ca2+ current produced by 3 microM Iso was 42 +/- 6% (mean +/- S.E.M.) and the response could be obtained repeatedly in the same cell. The concentration-response relationship could be fitted by a binding model with a Hill coefficient of 1 and a dissociation constant of 42 nM. 3. The effect of Iso on Ca2+ current was voltage dependent. Although potentiation of Ca2+ current by Iso was obvious between -30 and +10 mV, it was small or absent around +20 to +30 mV. Iso had little effect on the relationship between inactivation of the Ca2+ current and voltage obtained using a double-pulse protocol. 4. External application of forskolin, an adenylyl cyclase activator, or internal perfusion of cAMP or dibutyryl cAMP from the recording pipette, did not increase Ca2+ current and potentiation of Ca2+ current by Iso was observed repeatedly and was unchanged. 5. Internal perfusion of GTP gamma S or GDP beta S increased or did not affect the Ca2+ current and potentiation of Ca2+ current by Iso was unchanged and could be recorded repeatedly for about 20 min after rupture of the cell membrane. In addition, treatment of cells with the potent protein kinase C inhibitor, chelerythrine, had no effect on Ca2+ current or on potentiation of Ca2+ current by Iso. 6. These results suggest that the Ca2+ current in guinea-pig taenia caeci cells is potentiated by isoprenaline via mechanisms which do not involve either a cAMP pathway, a G-protein pathway or a protein kinase C pathway. The receptor involved appeared to be an atypical adrenoreceptor not blocked by either alpha- or beta-receptor blocking agents.

Tetramethylammonium activation of muscarinic receptors in cardiac ventricular myocytes.

Replacement of extracellular Na+ with tetramethylammonium (TMA) reduces the magnitude of the Cl- current activated by beta-adrenergic receptor stimulation in guinea pig ventricular myocytes. However, the effects of replacing Na+ appear to be associated with the presence of TMA, rather than the absence of Na+. Direct addition of TMA to extracellular solutions, without changing the Na+ concentration, was able to inhibit the Cl- current activated by isoproterenol (Iso) in a concentration-dependent manner. The concentration of TMA that caused half-maximal inhibition was 327 microM when the Cl- current was activated by 1 microM Iso and 29 microM when the Cl- current was activated by 0.03 microM Iso. The effect of TMA was also blocked by atropine, suggesting that TMA exerts its effect through stimulation of the muscarinic receptors. Furthermore, TMA inhibited the Iso-activated Ca2+ current, as would be expected for an effect involving muscarinic receptor stimulation. The response to complete Na+ replacement with TMA could not be overcome by increasing the concentration of Iso 1,000-fold, and direct addition of TMA was able to antagonize the Cl- current activated independently of the beta-adrenergic receptor, using forskolin and histamine. These results are consistent with the hypothesis that TMA does not exert its effects through a competitive mechanism at the beta-adrenergic receptor. It is concluded that TMA is able to antagonize adenosine 3',5'-cyclic monophosphate-dependent activation of ion channels in the heart through activation of muscarinic receptors.

The Effect of Zeatin and iso-Pentenyladenine on Root Growth of Pinus pinea L.

Summary Seedlings of Pinus pinea L. growing in half strength Hoagland's nutrient solution were treated for 24 h with different concentrations of zeatin (Z) and iso -pentenyladenine (iP). These cytokinins did not affect tap root length. Lateral root development was inhibited by Z. A low concentration of Z (10 −8 M) increased the root/shoot ratio and total root dry weight. Lateral root development was stimulated by iP. A concentration of 10-6M was the most effective and caused a 40 % increase in most root parameters measured.

Isoproterenol induces release of atrial natriuretic peptide from rat atrium in vitro.

To investigate the mechanism underlying the release of atrial natriuretic peptide (ANP) in in vitro condition, isolated, superfused rat atria were subjected to adrenergic, chronotropic, and mechanical stimulation. First administration of isoproterenol (Iso; either 10(-9) or 10(-6) M) caused a release of ANP, which was transient. Subsequent increments in concentration of Iso always resulted in a much lower release of ANP, despite the increased effects on the mechanical function of the atria. Stretching of the atria resulted in a transient release of ANP. Subsequent increments in stretching were followed by decreasing release of ANP. The total score of ANP in atrial tissue after Iso and stretching was not measurably depleted. Pacing the atria with increasing frequency did not induce release of ANP. Depolarization with 40 mM KCl abolished the release of ANP in response to Iso but not the release induced by stretch. In the presence of low external Ca2+, which abolished mechanical activity, both Iso and stretch could still induce release of ANP. Propranolol abolished the release of ANP by Iso but not that induced by stretching. Prazosin did not affect the release by either stretch or Iso. Stretching the atria 20 min after administration of Iso did not cause any further release of ANP. On the other hand, adding Iso 20 min after stretching induced a release of ANP. It is concluded that Iso and stretch cause a transient release from isolated strips of atria. The amount of ANP released is not related to the dose of Iso or to the load applied. Mechanisms involved in the release mediated by the two stimuli are different.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered cardiovascular responsiveness to adrenoceptor agonists in endurance-trained men

The influence of physical training on responses to intravenous infusions of phenylephrine (Phe) and isoproterenol (Iso) were investigated in 10 well-trained runners (WT) and 10 age-matched untrained controls (UT). The latter were reinvestigated after a 4-mo training period. The venous plasma Iso and Phe concentrations attained during infusions were lower in WT than in UT. Responses were related to the corresponding plasma concentrations. Phe-induced decreases and Iso-induced increases in heart rate were less pronounced (P less than 0.01) in WT than in UT. At venous plasma concentrations of 100 nM Phe and 0.8 nM Iso, the responses were -9 +/- 1 and 30 +/- 2, and -17 +/- 2 and 44 +/- 4 beats/min, respectively. Increases in blood pressures during Phe infusions were greater in WT than in UT (100 nM Phe: systolic 36 +/- 3 vs. 25 +/- 3 mmHg, P less than 0.05). The Iso-induced decrease in diastolic blood pressure was also more pronounced in WT (0.8 nM Iso: -29 +/- 3 vs. -15 +/- 2 mmHg, P less than 0.01). Iso-induced changes in systolic time intervals showed no consistent differences between training states. Increases in plasma adenosine 3',5'-cyclic monophosphate during Iso infusions were smaller (P less than 0.05) in WT than in UT, whereas increases in plasma glycerol were larger (P less than 0.05). Lymphocyte beta 2-adrenoceptor function and binding characteristics did not differ between training states. In summary, the present results indicate that beta-adrenergic vasodilator and alpha-adrenergic vasopressor responses are enhanced in endurance-trained subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactive effects of isoprenaline, forskolin and acetylcholine on Ca2+ current in frog ventricular myocytes.

1. Calcium currents (ICa) were measured in single cells isolated from frog ventricle using the whole-cell patch-clamp technique and a perfused pipette. The dose-dependent stimulatory effects of isoprenaline (Iso, 0.1-100 microM) and forskolin (Fo. 0.1-50 microM) on ICa were determined in the presence and absence of acetylcholine (ACh, 10 microM) and/or threshold concentrations of Fo (0.2 microM) and Iso (0.05 microM), respectively. EC50 (i.e. concentration of Iso or Fo at which the response was 50% of the maximum) and Emax (i.e. maximal stimulation of Ica expressed as percentage increase in ICa with respect to control) were measured under each condition. 2. ACh increased EC50 for the stimulatory action of Iso on ICa from 0.84 to 3.72 microM while it reduced Emax from 658 to 185%. Thus, ACh mainly reduced the efficacy of Iso to stimulate ICa. 3. ACh increased EC50 for the stimulatory action of Fo on ICa from 2.06 to 10.26 microM but only slightly reduced Emax from 893 to 778%. Thus, ACh mainly reduced the potency of Fo to stimulate ICa. 4. Intracellular perfusion with 100 microM of hydrolysis-resistant GTP analogues, GTP-gamma-S [guanosine-5'-O-(3-thiotriphosphate)] and Gpp (NH)p (5'-guanylylimido-diphosphate), had no effect on basal ICa but reduced by greater than 50% the stimulatory effect of 2 microM-Iso on ICa. 5. In the presence of Gpp(NH)p or GTP-gamma-S, Fo (3 microM) reversibly increased ICa by 490%, as compared to a 717% increase in control (GTP) intracellular solution. Although ACh could still inhibit Fo-stimulated ICa, the degree of inhibition was significantly smaller than in the presence of GTP. 6. Extracellular perfusion with low concentrations of a combination of Iso (33 nM) and Fo (330 nM) enhanced ICa to a much greater extent than did either agent alone at 3 times higher concentrations. Thus, low concentrations of Iso and Fo appear to increase ICa in a synergistic fashion. 7. ICa stimulated by a combination of Iso and Fo appeared to be more resistant to inhibition by ACh than when stimulated by either alone. It was the efficacy, rather than the potency, of ACh to inhibit ICa that was reduced upon dual stimulation of ICa. 8. In the presence of 0.2 microM-Fo, EC50 and Emax for the effects of Iso on ICa were 0.27 microM and 619%, respectively. By comparison with the effects of Iso alone, Fo reduced EC50 approximately 3 times with no significant change in maximal stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclic nucleotide metabolism in pineal homogenates.

Adenylate cyclase (AC) in pineal particulate fractions from rabbit, rat, cow, and the vole Microtus montanus was stimulated by L-norepinephrine (NE) and L-isoproterenol (ISO). NE stimulation of rabbit and bovine pineal AC was biphasic, with a plateau between 0.01 microM and 1.0 microM and additional stimulation by NE above 1.0 microM. Stimulation by different ISO concentrations gave a typical hyperbolic curve, and optimal stimulation by ISO exceeded that by NE. Melatonin decreased ISO and NE stimulation of AC 10-20%. Although, alpha-adrenergic agonists increase beta-agonist-mediated adenosine-3',5'-cyclic monophosphate (cyclic AMP) accumulation in intact pinealocytes, similar amplification of AC stimulation was not seen with broken-cell preparations. Most (60-70%) pineal guanylate cyclase (GC) was recovered in supernatant fractions after centrifugation of homogenates at 110,000 x g; this soluble GC was unaffected by potential agonists. Low concentrations (0.01-1 nM) of NE, ISO, and phenylephrine (PE) stimulated GC in impure and purified membrane fractions, but each inhibited at concentrations above 10 microM. All concentrations of ISO and NE inhibited GC in the presence of the alpha-agonist PE. Melatonin alone did not affect particulate GC, but L-ISO stimulation was not seen in the presence of equivalent concentrations of melatonin. The in vitro data are consistent with both alpha- and beta-receptor regulation of cyclic nucleotide metabolism in pinealocytes. Endogenous NE may differentially regulate cyclic AMP and guanosine-3',5'-cyclic monophosphate (cyclic GMP) in pineal; low NE concentrations that stimulate GC have only a slight effect on AC, but higher NE concentrations that inhibit GC maximally stimulate AC. Particulate GC and AC also were resolved by equilibrium centrifugation, to give several discrete peaks of enzyme activity. The results support the existence of several forms of AC and GC, which have different responses to adrenergic agonists.

Beta-adrenergic stimulation of adenosine-3',5'-monophosphate (c-AMP) accumulation and of prolactin and growth hormone secretion in rat anterior pituitary cell cultures.

The beta-adrenergic agonist 1-isoproterenol (ISO) (10(-9)-10(-7) M) provoked a prompt and profound increase of intracellular c-AMP accumulation in monolayer cultures of rat anterior pituitary. In superfused reaggregate cell cultures ISO also stimulated c-AMP outflow. The effect was blocked by propranolol and the highly selective beta 2-receptor blocker ICI 118.551. Epinephrine (E), norepinephrine (NE) and the highly selective beta 2-agonist zinterol (ZIN) also stimulated c-AMP accumulation. The order of potency ZIN greater than or equal to ISO greater than E much greater than NE together with the high potency of ICI 118.551 suggests the beta-effect is mainly through the beta 2-receptor subtype. The same concentrations of ISO strongly stimulated growth hormone (GH) release and, as previously shown, prolactin (PRL) release from superfused reaggregate cell cultures, but not luteinizing hormone or thyroid stimulating hormone release. Stimulation of PRL and GH release from these cultures was also induced by the adenylyl cyclase activator forskolin. Since interference of beta-adrenergic effects on contaminating fibroblasts or endothelial cells could be reasonably excluded, the present data suggest that beta-adrenergic stimulation of c-AMP accumulation in anterior pituitary cells elicits GH and PRL release.

Involvement of arachidonic acid metabolites in β-adrenoceptor desensitization: Functional and biochemical studies

The prolonged in vitro perfusion of rat lung with isoproterenol (Iso) induced a desensitization of β-adrenoceptors which was dose- and time-dependent. The decrease in functional responsiveness of rat lung parenchyma to the β-agonist correlated well with the loss of [ 3H]dihydroalprenolol ([ 3H]DHA) binding sites and adenylate cyclase activity after the β-adrenoceptor desensitization procedure. The cyclooxygenase inhibitor indomethacin prevented the β-adrenoceptor desensitization as was shown by the restored isoproterenol-induced relaxation in rat lung parenchyma strips and adenylate cyclase activity after the milder desensitization procedure. Inhibition of the arachidonic acid cascade at different levels with different compounds such as BW 755C and betamethasone prevented the desensitization of β-adrenoceptors. These findings suggest a role for arachidonic acid metabolites in β-adrenoceptor desensitization. The possible sites of action of arachidonic acid metabolites are also discussed in relation to the inability of indomethacin to prevent the desensitization of β-adrenoceptors that was induced by the higher Iso concentration used.

Cytotoxicity of isoproterenol to cultured heart cells: Effects of antioxidants on modifying membrane damage

Primary cultures of rat myocytes were used to study the cardiac damage induced by toxic doses of l-isoproterenol (ISO). Cultures were exposed to varying concentrations of ISO (2.4 × 10 −5, 1 × 10 −4, and 5 × 10 −4 m) for 0.5, 1.5, 4, and 12 hr. Mitochondrial membrane fragility, myocyte potassium content (as an index of sarcolemmal damage), and cellular glutathione content were used to evaluate cellular injury. A significant increase in mitochondrial fragility was observed 0.5 hr after treatment with 5 × 10 −4 M ISO. Lower doses caused an increase in mitochondrial fragility 1.5 hr after exposure. Longer durations of ISO exposure (4 and 12 hr) were necessary to decrease cellular potassium content. Glutathione levels were minimally affected by ISO. l-Ascorbic acid (5 × 10 −3 m) or sodium bisulfite (9.6 × 10 −4 m) were added to the cultures to determine if antioxidants prevent the toxicity caused by ISO. The presence of l-ascorbic acid or sodium bisulfite in ISO-treated myocyte cultures prevented the toxic changes in mitochondrial fragility and myocyte potassium content. The data indicate that antioxidants may be useful in reducing injury induced by toxic doses of ISO. Furthermore, mitochondrial injury may be involved significantly with the development of ISO-induced cardiotoxicity.

An in vitro study on the effects of isoprinosine on immune responses in cancer patients

The in vitro effects of ISO on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). For in vitro studies, an optimum concentration of ISO (100 μg/ml per 10 6 cells) was used to treat peripheral blood mononuclear cells. In the presence of ISO, all three parameters were restored to normal or near normal levels in those that were depressed. Under these preincubation conditions in vitro treatment of mononuclear cells from the peripheral blood of normal individuals with ISO had no effect on their activities in the three assays. Similar effects on these three immune parameters were observed when 24 h supernatants obtained from patients' mononuclear cells pretreated with ISO were employed in these assays.

Altered inotropic responsiveness to isoproterenol of hearts from spontaneously hypertensive rats during development.

The characteristics of the inotropic responses to isoproterenol (Iso) were investigated in isolated hearts from embryonic normotensive (NT) and spontaneously hypertensive (SH) Wistar-Kyoto rats at 14, 16, 18 and 20 days of gestation and from rats 3 and 10 weeks after birth and in ventricular strips prepared from hearts of newborn and 1-week-old rats. With rates of all preparations maintained constant by electrical stimulation, concentration and age dependent increases in contractility in response to Iso, capable of being blocked by propranolol, were observed. In embryonic hearts, irrespective of Iso concentration or embryonic age, similar effects were observed in hearts from NT and SH animals. However, in all postnatal preparations, the effects of Iso on the SH strain were quantitatively different from those on hearts of NT rats of the same age. As early as 12 hr after birth and through 10 weeks of age, most concentrations of Iso induced inotropic effects that were significantly greater in hearts of the SH than the NT strain and the slopes of the linear portions of the concentration-response curves were significantly steeper. These findings indicate that functional beta adrenergic inotropic receptors are present in the embryonic hearts of both strains and undergo changes during development that are strain dependent.

Negative inotropic effect of vanadate in ventricular myocardium in the presence of 3-isobutyl-1-methylxanthine or isoprenaline.

The influence of a low concentration of 3-isobutyl-1-methylxanthine (IBMX; 5μmol l−1) on the positive inotropic effect of vanadate (NH4VO3; 10–1,000 μmol l−1) and isoprenaline (ISO; 0.1–300 nmol l−1) was studied in electrically driven (frequency 1 Hz) papillary muscles isolated from guinea pigs. Furthermore the influence of maximally effective concentrations of IBMX (100μmol l−1), ISO (100nmol l−1) and dihydro-ouabain (DHO; 70μmol l−1) on the inotropic effect of NH4VO3 was investigated.

Uptake and O-methylation of isoprenaline in the rabbit ear artery.

Factors which influence uptake on O-methylation of 3H-isoprenaline (3HISO) by isolated segments of the rabbit ear artery were investigated. The tendency of the artery to accumulate unchanged amine was enhanced either when the O-methylation of ISO approached saturation at a high substrate concentration (6 mumol 1(-1) ISO), or when O-methylation was inhibited. Under these conditions, deoxycorticosterone acetate (DOCA) partially inhibited the accumulation of ISO. DOCA exerted a stronger inhibitory effect on O-methylation, but only at low ISO concentrations (0.2 and 0.8 mumol 1(-1)). The results are interpreted as evidence that (a)O-methylation in the intact artery is a saturable process which serves to limit the accumulation of 3HISO when the bathing concentration of the amine is low, and (b) DOCA exerts its effects by inhibiting extraneuronal uptake into the compartment possessing O-methylating activity. Analysis of the kinetics of efflux of 3HISO suggested that O-methylation was restricted to only one compartment, whereas unchanged ISO was accumulated within at least two compartments in addition to the extracellular compartment. Attention is drawn to a small but significant inhibitory effect of chronic sympathetic denervation on the accumulation, although not the O-methylation of ISO, raising the possibility that there may also be distribution of 3HISO within the sympathetic nerves.

Lipids of Recent sediments, Part II. Branched and cyclic alkanes and alkanoic acids of some temperate lacustrine and sub-tropical lagoonal/tidal-flat sediments

Analyses of the branched and cyclic alkane and alkanoic acid fractions from three temperate lacustrine and three sub-tropical alagoonal/tidal-flat sediments parallel earlier evidence from the corresponding straight-chain saturated and unsaturated fractions that the soluble organic material originates from both autochthonous and allochthonous sources. Among the lacustrine examples, that are thought to receive the highest contribution from blue-green algae occurs the highest relative abundance of 7- and 8-methylheptadecanes. In contrast, these components were not detected in the bottom sediment of the lake of lowest productivity. Varying concentrations of iso- and anteiso-alkanoic acids were found in the fractions studied in most detail. For example, the low concentrations of these components, obtained by solvent extraction alone of two of the sediments, parallel the distributions of the corresponding n-alkanoic acids in that they do not reflect a high bacterial and/or fungal contribution. The hydrocarbon fractions are, in general, characterised by an envelope of unresolved components and by triterpanes of the hopane type. The unresolved envelope probably originates from pollution of the sediments by fossil fuel products. The distribution of the triterpanes indicates that at least some of these components do not arise from contamination by petroleum products. Triterpenoid acids of the hopane type are present in certain of the sediments, indicating that these geolipids can be formed at the earliest stages of diagnesis.

Counter-ion effect on the unperturbed dimensions of polyelectrolytes

Calculations of the unperturbed dimensions of Na-polyacrylate have been carried out, for various concentrations of meso and racemic diads, allowing for coulombic interactions both between side charges within the chain and between side charges and the counter-ions. Contrary to previous calculations where the counter-ion was neglected, the present approach can explain the rather high experimental value of the characteristic ratio. Both the Monte Carlo method and the method suggested by one of the authors, based on the hypothesis of a conditional stereo chemical equilibrium within the chain, are employed; the results are in substantial agreement.