PubMed Health⌕ Search

Biomedical subjects

J Zaagsma

Publications and source records attributed to J Zaagsma.

At least 127 records · Page 7Linked to original sources
PubMed1984

Differentiation of functional adrenoceptors in human and guinea pig airways.

The nature of the beta-adrenoceptor population(s) mediating direct smooth muscle relaxation, inhibition of antigen-induced histamine release and inhibition of antigen-induced (leukotriene-mediated) smooth muscle contraction of human and guinea pig central and peripheral airways was investigated. Preferential blockade by beta 1- and beta 2-selective antagonists of the relaxation induced by beta 1- and beta 2-selective agonists, respectively, revealed the guinea pig tracheal smooth muscle relaxation to be mediated by both beta 1- and beta 2-adrenoceptors. Using a highly beta 2-selective antagonist, the NE-induced relaxation was split up biphasically into a beta 1- and a beta 2-component. In contrast, no such differential blockade was observed with the relaxation of the guinea pig lung parenchyma strip, neither with the human tracheal, main bronchus and respiratory bronchiolus smooth muscle, which are all mediated by homogeneous beta 2-adrenoceptor populations. Only in the guinea pig trachea did neuronal and extraneuronal uptake inhibitors produce pronounced left shifts of the NE- and ISO-induced relaxation curves, respectively, suggesting a causal relationship between noradrenergic innervation and the presence of the beta 1-adrenoceptor subpopulation in the airways. Using the same techniques, it was established that inhibition of antigen-induced histamine release from guinea pig lung and tracheal mast cells is mediated by homogeneous beta 2-adrenoceptor populations as well. In contrast to catecholamines, non-catecholamine beta-agonists such as fenoterol, clenbuterol and zinterol had a substantially higher apparent affinity for the inhibition of the anaphylactic (leukotriene-mediated) guinea pig tracheal contraction than for the inhibition of histamine release; the same was true for lung tissue, though the difference was less pronounced. With some non-catecholamine beta-agonists considerable selectivity both in central and peripheral airway preparations was observed for the inhibition of anaphylactic contraction as compared with smooth muscle relaxation.

Anaphylaxis↗
PubMed1983

Comparison of cyclic AMP-dependent phosphorylation of sarcolemma and sarcoplasmic reticulum from rat cardiac ventricle muscle.

1. The phosphorylation by cAMP and protein kinase I of rat cardiac sarcolemma (SL) and sarcoplasmic reticulum (SR) isolated from the same homogenate, was compared. 2. In both fractions, the phosphate incorporation is strongly dependent on the ATP and the membrane protein concentration. 3. SDS-gel electrophoresis reveals that in the SL preparation a protein of Mr = 24,500 and a glycoprotein of Mr = 17,500 are mainly phosphorylated, while in the SR fraction the main phosphate incorporation is found in a protein having a Mr = 37,000. 4. Isoprenaline stimulates the phosphorylation of SL but not of SR. Propranolol abolished that stimulatory action of isoprenaline completely, suggesting that the beta-adrenoceptor is involved.

Adenosine Triphosphate↗
PubMed1983

Comparison of functional beta-adrenoceptor heterogeneity in central and peripheral airway smooth muscle of guinea pig and man.

The nature of the beta-adrenoceptor population(s) mediating the relaxation of guinea pig and human airway smooth muscle was investigated. On the basis of a preferential blockade by beta 1- and beta 2-selective antagonists of the relaxation induced by beta 1- and beta 2-selective agonists, guinea pig tracheal strip relaxation was found to be mediated both by beta 1- and beta 2-adrenoceptors, the relative participation of which depending on the relative affinities of the agonist towards these two receptors. With highly selective antagonists the noradrenaline (NA)-induced relaxation could be split up biphasically into a beta 1- and a beta 2-component. In contrast, no such differential blockade was observed with the guinea pig lung parenchyma strip relaxation which is mediated by a homogenous beta 2-adrenoceptor population. On comparison of the tracheal, the spirally cut main bronchus- and intrapulmonary airway smooth muscle strips it could be shown that both the sensitivity of NA for neuronal uptake and the apparent affinity of the relaxation by NA decreased in the direction of the lung periphery. Using the same techniques it was ascertained that the relaxation of human tracheal smooth muscle (autopsy, obtained within 6 hours after death), main bronchus and intrapulmonary smooth muscle (operation) are mediated by homogenous beta 2-adrenoceptor populations. In addition, neuronal and extraneuronal uptake sites were not operative in these preparations, whether obtained from operation or from autopsy.

Animals↗
PubMed1981

Effects of adenosine and adenosine-analogs on adenylate cyclase activity in the rat adipocyte plasma membrane: comparison of the properties of the enzyme with Mn2+ and Mg2+ as divalent cations.

We investigated the influence of Mg2+ and Mn2+ on the effects of adenosine and some derivatives on basal adenylate cyclase activity in rat fat cell membranes as well as on enzyme activity stimulated by isoprenaline or sodium fluoride. Adenosine and derivatives modified in the ribose function were inhibitory, irrespective of the stimulant used, both in the presence of MgCl2 or MnCl2. Inhibition of basal and sodium fluoride stimulated adenylate cyclase activity was more pronounced in the presence of MnCl2 than in the presence of MgCl2. N6-substituted adenosine analogs proved to be inhibitory in the presence of 5 mM MgCl2, but in the presence of 1 mM MnCl2 the fluoride stimulated adenylate cyclase activity was potentiated, while basal and isoprenaline stimulated activity were not significantly inhibited. These effects of adenosine and derivatives could not be blocked by theophylline with or without guanyl nucleotides. The potentiating effect of N6-substituted adenosine derivatives on sodium fluoride activated adenylate cyclase is dependent on the structure of the N6-substituent and consists of an enhancement of Vmax in combination with a small decrease of the Km for MnATP2-, indicative of an allosteric effect on adenylate cyclase. No potentiation by N6-phenylisopropyladenosine of sodium fluoride stimulated cyclase was found on digitonin solubilized cyclase, while the inhibitory effect of adenosine was retained. The relevance of these findings is discussed in connection with the current hypothesis concerning the presence of two adenosine-sensitive sites on rat fat cell membranes.

Adenosine↗
PubMed1981

Fluorescence spectroscopic analysis of the hydrogen bonding properties of catecholamines, resorcinolamines, and related compounds with phosphate and other anionic species in aqueous solution.

Fluorescence spectroscopic analysis based upon the difference in fluorescent behaviour of several phenol, catechol and resorcinol derivatives in 0.2 M phosphate and water, at different pH values ranging from 7.4 to 1.0, produced evidence for the existence of complexes between phosphate anions and these compounds. This complex formation was also found with acetate, citrate and glutamate but not with sulphate and borate. A comparison of different ligand structures revealed that the complex formation observed with unsubstituted phenol, catechol or resorcinol was not influenced by ethyl substitution; however, ethylamine or ethanolamine substitution favoured the formation of the complex. The findings indicate the formation of 1:1 intermolecular complexes between mono- and dihydroxyphenethylamines and several anionic species with participation of two hydrogen bonds. The predictions of a theoretical model describing this interaction are confirmed by the experimental data. Association constants of isoprenaline with phosphate and glutamate were found to be 5.1 and 26.6 litres mol-1 respectively; for the complexes of m-tyramine and terbutaline with phosphate, association constants of 15.3 and 6.9 litres mol-1 respectively, were obtained.

Catecholamines↗
PubMed1980

beta-Adrenoceptor studies. 6. Further investigations on the hybrid nature of the rat adipocyte beta-adrenoceptor.

The nature of the rat adipocyte beta-adrenoceptor was studied in further detail using a selected series of tolamol-type beta-adrenoceptor antagonists. Isoprenaline antagonism by these compounds was evaluated on adipocytes, right atrium, left atrium and left hemidiaphragm of the rat. Adipocyte pA2 values were corrected for binding to bovine serum albumin determined separately for each antagonist. A strong correlation between adipocyte and diaphragm pA2 values was found with those antagonists which had an identical N-substituent but a different substitution pattern in the phenoxypropanolamine ring. This relationship was absent with those compounds which had the same 2-methylphenoxypropanolamine moiety but a different N-substituent. With the latter antagonists, however, adipocyte pA2 values correlated significantly with the two cardiac pA2 values. These results support the idea that the interaction site of the rat adipocyte beta-adrenoceptor for the aromatic moiety of arylethanolamines and aryloxypropanolamines has beta 2-characteristics whereas the alkanolamine side-chain interaction site has a beta 1-nature. Finally, it was ascertained that the apparently dualistic (beta 1 and beta 2) character of the rat adipocyte adrenoceptor is not due to the presence of both a beta 1- and a beta 2-receptor population on the fat cell plasma membrane.

Adipose Tissue↗
PubMed1977

The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum.

The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.

Animals↗
PubMed1977

Beta-adrenoceptor studies. 2. Effects of alkyl substitution on beta-adrenoceptor blocking, antiarrhythmic, and local anesthetic activities of 1,1'-(o-phenylenedioxy)bis(3-isopropylamino-2-propanol).

A series of bis(2-hydroxy-3-isopropylaminopropyl) ethers of nuclear-substituted catechols (1-7) has been synthesized and examined in vitro for beta-adrenoceptor blocking activity, antagonism of ouabain-induced arrhythmias, and local anesthetic activity. Both tracheal and right atrial beta-adrenoceptor blocking activity are markedly decreased by alkyl substitution in position 3 of parent catechol diether 1. Substitution in position 4 still lowers the affinity to cardiac arrhythmias and local anesthetic activity increases with introduction of alkyl substituents in the 3 as well as in the 4 position. In contrast with biological activities, the partition coefficient 1-octanol-phosphate buffer, pH 7.40, of 1 did not change significantly by 3- and 4-methyl substitution. Stepwise multiple regression analyses were performed using log P or pi values in combination with pKa(m), E8, or sigma. With cardiac beta-adrenoceptor blocking activity the optimal equation contained E8 and pi parameters, tracheal activity appeared to depend mainly on the E8 parameter, whereas for antiarrhythmic and local anesthetic activities the lipophilicity of the substituents appeared to be the determinant factor.

Adrenergic beta-Antagonists↗