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S Dion

Publications and source records attributed to S Dion.

61 records · Page 4Linked to original sources
PubMedDate not supplied

Characterization of pre- and postjunctional receptors for neurokinins and kinins in the rat vas deferens.

Neurokinins and kinins are potent stimulants of the rat vas deferens: they increase both the twitch response to electrical stimulation by facilitating transmitter release and the basal tone of the preparation by activating smooth muscle receptors. The two sites of action have been studied separately in the present experiments by using the prostatic for the prejunction site and the epididymal section of the vas deferens for the postjunction site. Receptors for neurokinins, characterized by the order of potency of agonists, appear to be of the NK-A type both at the pre- and postjunction level. Receptors for kinins are present also at both sites and are probably of the B2 type: they have been characterized by the use of agonists and, the B2 postjunction type has been convalidated with antagonists. These compounds could not be used for the prejunction receptor characterization, because they act as agonists. Receptor for angiotensin at the prejunction level are of the same type as in the cardiovascular and other systems.

Animals↗
PubMedDate not supplied

Substance P and neurokinins as stimulants of the human isolated urinary bladder.

Neurokinins are active stimulants of the human isolated urinary bladder. In a preliminary study, performed on bladders taken from four donors, we attempted the characterization of neurokinin receptors. It was shown that neurokinin A is more active than neurokinin B and substance P. Neurokinin receptors selective agonists were also tested and it was found that the most active compound was the NK-A selective agonist, [Nle10]NKA 4-10: A substance P antagonist was able to reduce the effect of neurokinin A but its affinity was rather low. This suggests that the receptor mediating the contraction of the human urinary bladder to neurokinins is of the NK-A (NK2) type. The action of neurokinins on the human urinary bladder appears to be a direct one and mediated by specific receptors different from those of other agents. On the contrary, kinins were found to be active through a new mechanism which was not influenced by either anti-B1 or anti-B2 receptor antagonists.

Adult↗
PubMedDate not supplied

Structure-activity studies of neurokinin A.

A structure-activity study on neurokinin A and its C-terminal fragment NKA (4-10) has been performed in order to find selective agonists for the NK-2 receptor and identify chemical modifications suitable for protecting the peptides from degradation, while maintaining activity. Five series of compounds have been prepared and tested: 1. the complete series of the L-Ala monosubstituted analogues of NKA; 2. a series of NKA fragments from the C- or N-terminal; 3. the complete series of NKA (4-10) analogues monosubstituted with beta-Ala; 4. a series of NKA (4-10) analogues with monosubstitutions in pos. 4, 8, 10 or multisubstitutions in two or more of the same positions; and 5. a series of 6 NKA (4-10) analogues monosubstituted with 1-amino,1-cyclohexane carboxylic acid residue. It has been found that the most selective agonists for the NK-2 receptor system are [beta Ala8]NKA (4-10) and [Nle10]NKA (4-10). Protection from aminopeptidase may be obtained by acetylation of the N-terminal amide of NKA (4-10), while partial protection from endopeptidases should be expected from the presence of beta-Ala in position 8. Conformational constraints induced with 1,amino,1-cyclohexane carboxylic acid residue gave weakly active compounds. Multiple substitutions reduce rather than potentiating the favorable effects of the corresponding monosubstituted compounds.

Animals↗
PubMedDate not supplied

Neurokinin A. A pharmacological study.

Discovered in 1983, the decapeptide neurokinin A has been shown to occur in several peripheral organs and to exert a variety of biological effects. In this article, we review the most sensitive and selective in vivo and in vitro tests which have been used in various laboratories to evaluate naturally occurring or synthetic neurokinin A. A comparison of the effects of neurokinin A and those of its mammalian homologues, substance P and neurokinin B as well as those of tachykinins and related peptides is presented in the frame of a study directed toward characterization of neurokinin receptors. Indeed, neurokinin A has been shown to be particularly active on a neurokinin receptor subtype, the NK-2. Structure-activity studies performed with neurokinin A and its fragments as well as with several analogues of both the decapeptide and the heptapeptide NKA(4-10) have brought to the identification of the minimum structure required for activation of NK-2 receptors. Selective agonists for this receptor have been identified, in particular [Nle10]-NKA(4-10) and [beta-Ala8]-NKA(4-10).

Animals↗