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Biomedical subjects

S Dion

Publications and source records attributed to S Dion.

At least 55 records · Page 3Linked to original sources
PubMed1985

Tachykinin receptors in smooth muscles: a study with agonists (substance P, neurokinin A) and antagonists.

Four preparations, sensitive to tachykinins, the guinea-pig urinary bladder, the rat duodenum, the hamster and dog urinary bladders have been investigated and compared with four other preparations described before: the guinea-pig ileum and trachea, the dog carotid artery and the rabbit mesenteric vein. On the basis of the order of potency of agonists, evaluated with substance P, physalaemin, eledoisin, kassinin and neurokinin A, the preparations can be separated into three groups, the guinea-pig urinary bladder and the dog carotid artery, in which substance P is the most potent and neurokinin A the weakest tachykinin, the rabbit mesenteric vein, the guinea-pig trachea and the rat duodenum, in which the opposite order is observed and the hamster and dog urinary bladders, in which kassinin is the most potent agonist. The guinea-pig ileum shows similar sensitivity to the five tachykinins. C-terminal partial sequences appear to be weaker than SP-(1-11) in three of the four new preparations, SP-(6-11) being first in the rat duodenum and slightly weaker than SP-(1-11) in the hamster and dog urinary bladders. Studies performed with antagonists or inhibitors of endogenous agents suggest that substance P and neurokinin A act directly on specific receptors. The effects of the two peptides are reduced by antagonists analogues of the sequence SP-(4-11). One of the antagonists, [D-Pro4,Lys6,D-Trp7,9,10, Phe11]SP-(4-11) has been shown to be competitive against substance P and neurokinin A in the guinea-pig ileum, the guinea-pig urinary bladder and the rat duodenum. This compound, shows definitely higher activity against neurokinin A and kassinin, compared to substance P in various preparations. [D-Tyr4,D-Trp7,9,Nle11]SP-(4-11) is the most potent tachykinin antagonist in the hamster and dog urinary bladders. In these preparations, the antagonists act also against substance P, but with lower affinity. These findings with antagonists support the indication, emerged from the order of potency of agonists, that tachykinins may act on two and possibly three different receptor types.

Animals↗
PubMed1985

Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium.

Peptides and non-peptides acting as vasoconstrictors or vasodilators have been tested in dog isolated carotid arteries with and without endothelium and in the presence and absence of a variety of antagonists and inhibitors of endogenous substances. It has been found that substance P and several other tachykinins, bradykinin, neurotensin, bombesin and acetylcholine relax the isolated artery only when the endothelium is present, while VIP, isopropylnoradrenaline, adenosine, histamine, prostaglandins E1 and E2, glucagon and insulin relax and angiotensin, vasopressin, oxytocin, 5-HT and noradrenaline contract the isolated vessel, no matter whether the endothelium is present or not. Peptide and non-peptide antagonists have been used with success to show that vasoconstrictors and vasodilators act on specific receptors, since their effects are reduced in the presence of antagonists, specific for one or another of the various agents. Inhibitors of the arachidonic acid cascade only reduce the effect of acetylcholine, suggesting that at least two different mechanisms are involved in the endothelium-mediated relaxation of arterial smooth muscles to peptide and non-peptide agents. The results summarised in this paper suggest that the site of action of several vasodilators is the endothelium, while other vasodilators and all the vasoconstrictors influence the arterial vessels tone presumably by acting on the smooth muscle cells.

Animals↗
PubMed1985

Activities and antagonism of bombesin on urinary smooth muscles.

Substance P (SP), bombesin (BB) and bradykinin (BK) induce dose-dependent contractions of the rat and guinea-pig urinary bladders (RUB, GPUB). The three peptides differ in their affinities and intrinsic activities, BB being the most active both in terms of affinity (pD2 8.33 in the RUB and 8.83 in the GPUB), SP (8.03 and 7.53), BK (7.20 and 7.35), and of intrinsic activity. The myotropic effects of BB and SP are not modified by antagonists of neurotransmitters and autacoids that occur in peripheral organs, but that of BK is reduced in the presence of both the cyclooxygenase and lipoxygenase inhibitors. Undeca- and octapeptide antagonist analogues of SP and SP-(4-11) show similar pA2 values against BB and SP and are inactive against BK: the compound [D-Pro4, Lys6, D-Trp7,9,10, Phe11] SP-(4-11) is however more active (pA2 6.36 in the RUB and 6.18 in the GPUB) against BB than against SP (pA2 5.33 and 5.65 respectively), while it is inactive against BK. These results confirm data from the literature as to the ability of some tachykinin-antagonists to act against BB and shows chemical modifications that can improve the antagonist potency selectively against BB.

Animals↗
PubMed1985

Substance P antagonists showing some selectivity for different receptor types.

Five antagonists have been used against substance P (SP) and neurokinin A (NA) in isolated smooth muscle preparations containing either SP-P (the guinea pig ileum (G.P.I.), the dog carotid artery (D.C.A.) or SP-E receptors (the rat duodenum (R.D.), the dog (D.U.B.) and hamster urinary bladders (H.U.B.]. [D-Pro4,D-Trp7,9,10, Phe11]SP-(4-11) was found to be selective for SP-P receptors, since it showed high affinity both against SP and NA, on the G.P.I. and D.C.A., while it was found to be inactive on some SP-E receptor systems (D.U.B., H.U.B.) and very weak in others (R.D.). Two octapeptide antagonists, modified in position 6, [D-Pro4,Ala6,D-Trp7,9,10,Phe11]SP-(4-11) and [D-Pro4,Lys6,D-Trp7,9,10,Phe11]SP-(4-11) showed some selectivity for SP-E receptors since they acted as full agonists on one SP-P preparation (the D.C.A.) and the first compound contracted also the G.P.I. In addition to being pure antagonists on the D.U.B., H.U.B. and on the R.D., the two octapeptides showed a higher potency against the SP-E stimulant NA, compared to SP, in the R.D. Two undecapeptide antagonists were active against SP and NA on both SP-P and SP-E receptor preparations and therefore were less discriminative than the octapeptides. They were however more active against NA on the R.D., similar to the octapeptides modified in position 6. It is concluded that: (a) both agonists and antagonists appear to be useful for the characterization of tachykinins receptors; (b) either the whole N-terminal portion of SP or a shorter sequence, modified in position 6, increase the antagonist affinity against NA in the SP-E receptor system of the rat duodenum.

Angiotensin II↗