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S Reissmann

Publications and source records attributed to S Reissmann.

At least 37 records · Page 2Linked to original sources
PubMed1995

New photoaffinity labelled agonists of bradykinin.

Several photoaffinity labelled agonists of the peptide hormone bradykinin (BK) were synthesized by solid phase methods. Their biological activities and binding affinities were determined in both the isolated rat uterus (RUT) and guinea pig ileum (GPI). As photoreactive groups p-benzoyl-phenylalanine (Bpa) and the arylazides azidobenzoic acid (ABA) and azidosalicylic acid (ASA) were attached to the N-terminus of the BK agonists. In addition, Bpa was incorporated at different positions of the BK sequence. Three different types of BK agonists were used. Firstly, the photolabels ASA and ABA were attached to BK or to Lys-BK (kallidin). Secondly, tyrosine containing BK analogues, suitable for radioiodination, were labelled. This series is derived from the naturally occurring analogue phyllokinin [BK-Ile-Tyr(SO3H)] and from BK analogues with tyrosine at position 0 and 3. The third series includes several analogues with D-N-methyl-phenylalanine (D-NMe-Phe) at position 7, which selectively discriminate between the RUT and GPI bradykinin B2 receptors. Among the photoaffinity labelled BK agonists, the iodinatable Lys(ASA)-BK (50.8% on RUT, 73.0% on GPI), ASA-BK (26.3% on RUT), Bpa-BK-Ile-Tyr (13.6% on RUT, 14.0% on GPI) and the iodinated [D-Bpa-1, 3-I-Tyr0]-BK (15.5% on RUT, 19.0% on GPI) retained a relatively high biological activity compared with BK (100%). Thus, although BK agonists are known to allow only very restricted modifications without a strong reduction in biological activity, these compounds should be useful candidates for receptor labelling.

Affinity Labels↗
PubMed1995

Potent photoaffinity labelled and iodinated antagonists of bradykinin.

Continuing the studies on photoaffinity labelled analogues of the peptide hormone bradykinin (BK), several labelled antagonists were synthesized and characterized regarding their biological activities on rat uterus (RUT) and guinea pig ileum (GPI). The photoreactive amino acid p-benzoyl-phenylalanine (Bpa) was incorporated in potent, iodinated BK analogues at positions -2, -1, 0 and 7. The newly synthesized BK antagonists were derived from HOE 140 ([DArg0, Hyp3, Thi5, D-Tic7, Oic8]-BK) or [D-Phe7]-BK. Because the application of Bpa requires an additional group for the introduction of 125I, iodinated tyrosine was inserted at different positions as a model for radioiodination. Suitable positions for incorporation of tyrosine residues are -1, 0, 3 and 7, whereas the compound with 3-I-Tyr at position 4 had only a low biological activity. The antagonists obtained by modification of HOE 140 generally retained a high antagonistic potency. In this group [D-Bpa-2, 3-I-D-Tyr-1, D-Arg0, Hyp3, Thi5, D-Tic7, Oic8]-BK (pA2 values 8.06 on RUT and 8.15 on GPI) and [Bpa-1, D-Arg0, 3-I-Tyr3, Thi5, D-Tic7, Oic8]-BK (pA2 values 7.55 on RUT and 8.07 on GPI) belong to the most active compounds. The incorporation of D-Bpa at position 7 also resulted in potent analogues. The antagonists [3-I-Tyr-1, D-Arg0, D-Bpa7]-BK (pA2 on RUT 7.69) and [3-I-Tyr-1, D-Arg0, D-Bpa7, Oic8]-BK (pA2 on GPI 7.53) are an alternative to the N-terminal modified HOE 140 analogues. Compounds with D-Bpa7 act as pure competitive antagonists, whereas the HOE 140 derivatives show a mixed antagonism. The comparison of the results between photoaffinity labelled agonists and antagonists suggests that modifications in the series of BK antagonists were better tolerated.

Affinity Labels↗
PubMed1992

Hydrolysis of peptide esters by different enzymes.

The combined use in peptide synthesis of the Fmoc-group with methyl, benzyl or p-nitro benzyl esters is not practical because of the elimination of the Fmoc-group under basic conditions and by catalytic hydrogenation. Nevertheless the solution synthesis of peptides requires those combinations in some cases. For this purpose we have investigated enzymatic hydrolysis of some tri and tetrapeptide esters. The hydrolysis were carried out under pH-control. We measured deprotection of the carboxyl group by thermitase, porcine liver esterase, carboxypeptidase A and alpha-chymotrypsin. The main problems are to suppress proteolytic degradation of the peptide bond and to bring the protected peptides into solution. To solve both problems we used dimethylformamide and dimethylsulfoxide as cosolvents. The ratios between esterolytic and proteolytic activity were estimated under various cosolvent concentrations. Advantages of this method are to avoid side reactions of alkaline instable side chains (e.g. asparagine, glutamine), cleavage of base labile protecting groups and racemization by alkaline saponification. The enzymatic deprotection was followed by HPLC, HPTLC and titration. On a preparative scale this method gives good yields and sufficiently pure products.

Amino Acid Sequence↗
PubMed1992

[Peptide inhibitors of the renin-angiotensin system. 2. Polymer-bound tri-, penta- and nonapeptide inhibitors of angiotensin converting enzyme].

Inhibitors of the angiotensin converting enzyme (ACE, EC 3.4.15.1) are important in the treatment of the high blood pressure. The therapeutically used drugs captopril, enalapril and ramipril are enzymatic stable short pseudo-peptides. They are stabilized against enzymatic degradation and therefore usefully for oral application. But for some indications e.g. post operative treatment and shock therapy well dosed infusions are needed. For this purpose we attached nona-, penta- and tripeptide inhibitors of the ACE to immunologically inert dextran polymers. The inhibitors are derived as well from the bradykinin potentiating nonapeptide BPP9 alpha (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) and the bradykinin potentiating pentapeptide BPP5 alpha (Pyr-Lys-Trp-Ala-Pro), both originally isolated from snake venoms, as from acylated tripeptides with the structure Acyl-AA1-Arg-Pro. We estimated the influence on the biological activity of two different linkers to the dextran polymers. The coupling to the polymer was achieved on the one hand via the aldehyd moiety (DAD-AK) and on the other hand by the carboxyl residue (KMD). In the case of DAD-AK-polymers the condensation of the peptides was performed by the N-hydroxysuccinimide ester of the polymer. Because of the instability of the KMD-OSU in this case water soluble carbodiimides are used. The polymer bound peptides inhibit the isolated ACE, but in the most cases with a reduced activity. Only the tripeptide DPhe-Arg-Pro has a enhanced activity in the polymer bound state. The polymer bound inhibitors show a prolongated action on normotensive rats by intravenous application.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Antagonist binding reveals two heterogenous B2 bradykinin receptors in rat myometrial membranes.

In rat myometrial membranes, two bradykinin binding sites with K1 values of 18 pM and 5.6 nM were identified. Three potent bradykinin antagonists were tested for their ability to compete for [3H]bradykinin binding. Two of them, D-Arg[Hyp3,Thi5.8,D-Phe7]bradykinin and [Hyp3,Thi5.8,D-Phe7]bradykinin, also bound to both the high- (KH) and the low-affinity (KL) site whereas [Thi5.8,D-Phe7]bradykinin identified only the low-affinity bradykinin receptor. There is a close correlation between the antagonistic potencies and the KL site affinities.

Animals↗
PubMed1990

A high-affinity bradykinin receptor in membranes from rat myometrium is coupled to pertussis toxin-sensitive G-proteins of the Gi family.

In rat myometrial membranes, two 3H-Bradykinin binding sites with KD values of 16 pM and 1.0 nM were identified. Employed at pM concentrations, bradykinin stimulated high affinity GTPases. This effect was abolished by the bradykinin antagonist, [D-Arg(Hyp3-Thi5,8, D-Phe7)]bradykinin (10 microM), and by treatment of membranes with pertussis toxin. Myometrial membranes contained two pertussis toxin substrates of 40 and 41 kDa, which corresponded immunologically to alpha-subunits of Gi-type G-proteins. The faster migrating substrate was tentatively identified as Gi2 alpha-subunit. The electrophoretic mobility of the slower migrating Gi alpha-subunit was very similar to that of the Gi3 alpha-subunit. Go alpha-subunits were not detected. Thus, in uterine smooth muscle, G-proteins of the Gi-family (Gi2, Gi3) couple high-affinity bradykinin receptors to their effector enzymes.

Adenosine Diphosphate Ribose↗
PubMed1990

Bradykinin inhibits rat myometrial adenylate cyclase activity via a high-affinity receptor.

Bradykinin (BK) which contracts the rat uterus inhibited at subnanomolar concentrations rat myometrial adenylate cyclase stimulated by NaF or guanyl nucleotides by about 40%. The effect was maximal at about 10 to 100 pM. At a higher concentration (100 nM), bradykinin was ineffective. Together with recently presented results these data suggest that in rat myometrium the adenylate cyclase may be coupled by a G12/G13-type G-protein to a high-affinity BK receptor.

Adenylyl Cyclases↗
PubMed1989

Bradykinin action in the rat duodenum: Ca2(+)-dependent effects of bradykinin on the activity of particulate guanylate cyclase.

The nonapeptide bradykinin has been found to exert opposite effects on cGMP synthesis in a plasma membrane fraction from the rat duodenum. In the absence of exogenous Ca2+ BK increased the activity of the duodenal particulate guanylate cyclase which is decreased, in contrast, in a medium containing 1 mM exogenous Ca2+. In a Ca2(+)-free medium, on the other hand, both BK effects are completely prevented. The results suggest a presumable role of pGC in BK signal transmission in the rat duodenum with calcium ions as a mediator and/or essential cofactor.

Animals↗
PubMed1988

Bradykinin action in the rat duodenum: influence of a duodenum contracting bradykinin partial sequence on the cAMP level.

A modified bradykinin partial sequence (PP) contracts the isolated rat duodenum, inhibits the adenylate cyclase activity and decreases the cAMP level. These effects are dependent on the presence of free Ca++. The PP acts in contrast to bradykinin itself, which relaxes the rat duodenum and stimulates adenylate cyclase. The results further support the involvement of both cAMP and Ca++ in bradykinin action on rat duodenum smooth muscle.

Adenylyl Cyclases↗
PubMed1987

Bradykinin action in the rat duodenum: receptor binding and influence on the cyclic AMP system.

Bradykinin binds to a single class of binding sites at rat duodenum plasma membranes. In the presence of endogenous calcium and at low bradykinin concentrations the receptor activation is followed by a stimulation of adenylate cyclase activity and the elevation of the cAMP level. In the absence of calcium and at high peptide concentrations the cAMP level is lowered via both inhibition of adenylate cyclase and stimulation of cAMP-phosphodiesterase. These different changes in the cAMP level might be correlated with the biphasic pharmacological action of bradykinin in the rat duodenum. The results suggest that one type of bradykinin (B2) receptor is able to initiate several effectuation mechanisms.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

[Synthesis and analysis of conformationally restricted analogs of peptide inhibitors of the angiotensin-converting enzyme].

To investigate conformations of peptide inhibitors of the angiotensin-converting enzyme in the enzyme-inhibitor complex, the synthesis, studies of inhibitory activity, and conformational calculations of analogues of bradykinin-potentiating peptides with N-methylalanine or D-alanine in place of L-proline or L-alanine residues have been carried out. All the analogues showed a sharp decrease of inhibitory activity in comparison with the natural peptides, that might be considered as an indirect confirmation of the earlier proposed "conformation of inhibition" of the above-mentioned peptides.

Amino Acid Sequence↗
PubMed1985

[Synthesis and effect of affinity-labeled analogs and partial sequences of the bradykinin potentiating nonapeptide BPP9 alpha (teprotide)].

Affinity labeled analogues and partial sequences of the bradykinin potentiating nonapeptide BPP9 alpha inhibit the BPP9 alpha induced potentiation of the bradykinin action on the isolated guinea pig ileum. The labeled nonapeptides are more active than the labeled partial sequences. The inhibition of the potentiating action of BPP9 alpha demonstrates, that the influence on bradykinin action is not only a result of the inhibition of peptidyl dipeptide hydrolase.

Affinity Labels↗
PubMed1979

[On the mode of action of bradykinin on smooth muscle (author's transl)].

At extremely low concentrations, in the picomole and the nanomole range, bradykinin produces contraction and relaxation of smooth muscle in the gastrointestinal and the urogenital tract. At the target organ, bradykinin interacts with discriminator proteins of the plasma membranes and triggers, via changes in certain membrane functions, its biological response:--The binding to the discriminator makes specific conformative and constitutional demands on the nonapeptide. The binding results from an angular conformation which exists in the solution. The complete sequence is responsible for this specific conformation. Consequently, the biological activity of partial sequences is low. The conformational analysis of analogues used in studies on the mechanism of action showed but slight differences from bradykinin. The interaction of these analogues with the discriminator protein is disturbed to a varying extent by modifications at positions 1, 5, 8 and 9 in the side chains. The affinity for the discriminator is affected, dependently on the respective configuration, by substitution on the beta-C atom in the two phenylalanine residues.--Bradykinin is not only bound to, but also degraded at, the plasma membranes of the rat uterus and duodenum. The bradykinin-degrading enzyme has been characterized as a kininase II with the aid of various inhibitors. The conformative and configurative prerequisites decisive for enzymatic degradation are others than those decisive for binding to the discriminator.--The changes in the activities of the membrane-bound adenylate and guanylate cyclases (produced by the bradykinin-discriminator complex) that take place at the rat duodenum and uterus in the presence of extracellular calcium ions contrast with each other: At the duodenum, the ratio between these two cyclic nucleotides is changed in favour of adenylate cyclase; and at the uterus, in favour of guanylate cyclase; Substances which increase or decrease the cAMP level may also potentiate or inhibit the relaxation of the duodenum. These bradykinin-induced changes in enzyme activity must be considered in connection with other effectors, e.g. prostaglandins and calcium ions.--The calcium-ion-dependence of the effect of bradykinin on the guinea-pig ileum and the rat uterus indicates the importance of these ions as additional second messengers. Bradykinin stimulates the influx of calcium ions into the ileum; it is ineffective if no extracellular calcium ions into the ileum; it is ineffective if no extracellular calcium ions are available. It seems that intracellular and membranal calcium is mobilized in the uterus, which is evidenced by results from experiments with EGTA on the isolated organ and by the release of calcium from plasma membranes after application of bradykinin. It is assumed that the observed changes in membrane functions are induced by the peptide-discriminator complex simultaneously and not in the form of a causal chain.

Animals↗
PubMed1977

Bradykinin action in the rat duodenum through the cyclic AMP system.

Activators of the adenylate cyclase or inhibitors of the cAMP-phosphodiesterase, respectively, potentiate the bradykinin-induced relaxation of the rat duodenum, whereas imidazole as a stimulator of the cAMP-phosphodiesterase reduces the relaxation. The experiments indicate a linkage between the adenylate cyclase system with the biological action of bradykinin on the rat duodenum. In contrast, no similar effect has been observed on the rat uterus.

3',5'-Cyclic-AMP Phosphodiesterases↗