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H P Bär

Publications and source records attributed to H P Bär.

At least 19 recordsLinked to original sources
PubMed1977

Characteristics of the relaxant response of adenosine and its analogs in intestinal smooth muscle.

Several characteristics of the relaxant response of the isolated longitudinal muscle of the rabbit small intestine in response to the administration of adenosine and related compounds are studied. Following administration of adenosine or ATP the preparation responded with a rapid initial suppression of spontaneous contractile activity followed by a secondary sustained phase of inhibition of lower magnitude. Cumulative application of relaxant doses of adenosine or ATP caused a lesser total response than that obtained by single application of the cumulative dose. Neither procaine, lidocaine or guanethidine antagonized the responses to adenosine or ATP and the responsiveness of muscles obtained from reserpinized animals appeared unchanged. A number of adenosine derivatives and analogs was tested for the ability to relax the muscle. Generally, compounds containing a primary or secondary 6-amino group acted as agonists with the exception of 8-bromoadenosine. Those nucleosides found to be inactive did not modify the responsiveness of the muscle to adenosine. Responses to adenosine and ATP were not appreciably modified by papaverine, imidazole, dipyridamole, 6-(p-nitrobenzylthio)-purine riboside. Antagonism was observed, however, with phentolamine and theophylline. Theophylline at 100 muM inhibited responses to adenosine over a wide dose range; this antagonism was surmountable by high doses of adenosine. 1-Methyl-3-isobutylxanthine did not antagonize adenosine responses. A number of 1,3-alkyl-6-thioxanthines did not modify the adenosine response at doses that did not show any direct action. The results supported the concept of an extracellular receptor site of adenosine and its analogs and the absence of an indirect mechanism of action via nerve stimulation.

Adenosine↗
PubMed1977

Effects of adenosine and related compounds on adenylate cyclase and cyclic AMP levels in smooth muscle.

The hypotheses were tested that the relaxant effect of adenosine and related compounds in the longitudinal muscle of the rabbit small intestine involves interaction with adenylate cyclase and/or the elevation of tissue cAMP levels. Adenylate cyclase was prepared by gentle homogenization of an isolated smooth muscle cell fraction obtained after collagenase digestion of longitudinal muscle strips. A number of analogs and derivatives of adenosine possessing a primary or secondary 6-amino group were found to inhibit the enzyme similarly to adenosine; however, there was no correlation between compounds known to relax the intact tissue and the existence, or the degree of, cyclase inhibition. Isolated muscle strips were exposed to adrenaline, isoprenaline, adenosine or ATP, at doses causing 30-60% relaxation, for 60 sec prior to sampling and analysis of cAMP content. While small increments in cAMP levels were found after administering adrenaline or isoprenaline, no change was found with adenosine in the absence or presence of theophylline of 1-methyl-3-isobutylxanthine. Neither adenylate cyclase inhibition nor changes in cAMP levels appear to be part of the mechanism of the smooth muscle relaxant action of adenosine or ATP.

Adenosine↗
PubMed1976

The relaxant effect of adenosine-5'-alpha, beta-methylenediphosphonate on the longitudinal smooth muscle of the rabbit ileum.

The response pattern of the isolated longitudinal muscle of the rabbit ileum to adenosine-5'-alpha, beta-methylenediphosphonate (APCP) was found to differ from that caused by adenosine or ATP in that the rapid initial phase of relaxation is absent and that at doses above 10 muM a secondary increase of contractile activity occurs in the continued presence of the nucleotide. This secondary phase was attenuated after indomethacin pretreatment and reestablishement of tone with acetylcholine. Theophylline did not modify APCP-induced relaxations while effectively antagonizing those caused by adenosine. It appears that APCP acts via a receptor site or pathway distinct from that of adenosine or ATP.

Adenosine↗
PubMed1976

Adenylate cyclase, cyclic nucleotide phosphodiesterase, and norepinephrine binding in rat heart membranes.

The method of Kidwai et al. (1971. Biochem. Biophys. Res. Commun. 45:901) offers a rapid and simple technique for the preparation of membrane fractions from rat heart, using sucrose density centrifugation of a 100,000x g pellet. We have investigated the distribution of adenylate cyclase, cyclic AMP phosphodiesterase, and norepinephrine binding activity in these fractions. Specific activity of adenylate cyclase was high in the plasma membrane (PM) and sarcoplasmic reticulum, as well as the nuclear (N) fractions, but 80-90 percent of the total activity was found in the N fraction. Epinephrine stimulation of adenylate cyclase was present in all fractions but did not exceed 25 percent of basal activity. The activity in the mitochondrial fraction was low and insensitive to epinephrine. About 10 percent of phosphodiesterase activity was found in the 100,000 x g pellet. After density gradient centrifugation, 70 percent of this portion was recovered in the N fraction, with the highest specific activity present in the PM fraction. Binding of [3H] norepinephrine was measured by a membrane filtration technique. Binding activity was found in all fractions, and it paralleled roughly the distribution of adenylate cyclase. However, only about 25-30 percent of the binding was blocked by propranolol, except in the PM fraction where binding was not prevented by this drug. Further, a comparison of adenylate cyclase activities with norepinephrine binding yields a turnover number for the enzyme of the order of 10(-2) sec-1, assuming a 1:1 relationship between beta-adrenergic recptor and adenylate cyclase. Since this value seems unrealistic, we suspect that either the binding activity measured is unrelated to the beta-adrenergic receptor or the receptor to cyclase ratio is considerably larger than unity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

On the accumulation of adenosine 3':5'-monophosphate in Ehrlich cells and adenylate cyclase desensitization in response to epinephrine.

The time course of the action of epinephrine on cAMP levels in isolated mouse Ehrlich ascites cells was studied. Following the addition of hormone (10(-7) to 10(-4) M), cAMP levels reached a maximum within 1 min and declined to about 2 fold basal levels within 10-20 min. The decline phase was not due to the metabolism of epinephrine or accumulation of an inhibitor in the medium. Experiments involving timed additions of theophylline to epinephrine-treated cells suggested that the rate of cAMP synthesis declined progressively with time. Cells treated with epinephrine and then washed free of hormone were shown to be refractory to hormonal stimulation of cAMP levels. Adenylate cyclase prepared from epinephrine-treated cells was shown to exhibit decreased sensitivity to the hormone in in vitro incubations. Resensitization of the enzyme could be achieved by washing pretreated cells free of epinephrine and reincubating them for 1/2 to 2 h. Neither desensitization nor resensitization were prevented by cycloheximide or actinomycin D. Desensitization could not be induced by incubating cels with dibutyryl-cAMP. The desensitization phenomenon is considered to be a mechanism whereby cells protect themselves against the possible harmful effects of high levels of cAMP maintained over a long period of time.

Adenylyl Cyclases↗
PubMed1975

An extended Scatchard analysis for competitively bound ligands and its application to cyclic adenosine-3',5'-monophosphate and cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate binding to beef skeletal muscle protein.

A method for determining the dissociation constants of ligands and ligand analogs is described. It is based on competition binding studies in the presence of an isotope-labeled, or otherwise measurable, ligand and suitable analog concentrations. The steps used are determination of (1) the maximal amount of radioactive ligand that can be bound, (2) the slopes and intercepts from Scatchard plots at different analog concentrations and (3) the values for the dissociation constants of radioactive ligand and ligand analog from replots of the reciprocals of the slopes and intercepts obtained from the Scatchard plots. Application of the method to a cyclic AMP-binding protein from beef muscle is demonstrated, yielding dissociation constants of 2.10-9 M for cyclic (3H) AMP and cyclic AMP, and 3.10-5 M for cyclic 5'-amido-5'-deoxyadenosine-3', 5'-monophosphate.

Amides↗
PubMed1975

Effects of Lubrol detergents on adenylate cyclases.

The nonionic detergent Lubrol WX showed diverse, concentration-dependent effects onbasal and stimulated adenylate cyclases. Above concentrations of 0.001-0.01% Lubrol WX, the basal activity of cyclase from Ehrlich ascites cells was inhibed about 50%, and that from rat fat cells was doubled. In both cases, hormonal sensitivity was lost at 0.01%. These effects were reversed upon dilution of the detergent. It is suggested that solubilization of adenylate cyclases at such low concentrations of Lubrol should be attempted since it is conceivable that loss of hormone sensitivity may then be reversible. Different Lubrol-type detergents may also offer centain advantages, since Lubrol PX effects were not identical with those of Lubrol WX.

Adenylyl Cyclases↗
PubMed1975

Inhibition of extracellular and purified 5'-nucleotidase from rat heart.

5'-Nucleotidase in perfused rat hearts, accessible to extracellular substrate [14C]-AMP contained in the perfusate, was compared to a partially purified 5'-nucleotidase from the same organ. Both activities were inhibited by ATP and, more effectively, by the ADP analog adenosine-alpha, beta-methylene diphosphate (APCP). The isolated enzyme showed a competitive inhibitor constant of 5.4 x 10(-8) M for APCP (Km of AMP = 1.4 x 10(-5) M). Although both activities were effectively inhibited by APCP, insufficient knowledge about the selectivity of this agent as a nucleotidase inhibitor does not permit a conclusion on whether or not the extracellular activity is identical to the partially purified enzyme.

Adenosine Diphosphate↗