Effects on Smooth Muscle and Blood Vessels of Polypeptides Related to Bradykinin and to Kallidin

Abstract

provide evidence to support the hypothesis that triamterene acts in the distal tubule to reduce Na reabsorption. While this drug acts in the same area of the tubule as aldosterone and causes effects on sodium reabsorption opposite to those attributed to aldosterone( 9 ) , competitive inhibition cannot be inferred.The fact that triamterene causes a natriuresis in adrenalectomized rats and dogs indicates that the drug acts by other mechanisms than aldosterone antagonism.There were no consistent changes in urine flow rate, free flow urine Na concentration, and proximal urine Na concentration in 4 experiments where stop flow studies were done before and after triamterene. While proximal tubular events are not as easily assessed by the stop flow method (6), there is no evidence to support the idea of a proximal tubular action of the drug.Summary. The pteridine compound triamterene was studied in l l dogs using the stop flow method. These data support the hypothesis that the site of action of triamterene is the distal tubule of the kidney and that triamterene produces its natriuretic effect by reducing Na reabsorption in this area.No evidence was obtained for a proximal renal tubular effect.The authors wish to thank bt. W. S. Wilde for helpful criticism on stop flow and for the use of laboratory facilities and grant support in his absence.

Further Studies of the Sensitization of Smooth Muscle to the Action of Plasma Kinins by Proteolytic Enzymes

“…In comparing the relative potency of the bradykinin analogues, 6-glycine bradykinin and 7-glycine bradykinin, it appeared that their effect on the guinea-pig isolated ileum is considerably weaker than that on guinea-pig blood pressure and rat isolated uterus preparation. In the latter, both peptides showed an activity of the same order of magnitude as bradykinin (Rubin, Waugh, Laffan, O'Keefe & Craver, 1963), whilst on guinea-pig blood pressure 6-glycine bradykin has been reported to be even more effective than bradykinin (Erdos, Wohler & Levine, 1963).…”

“…In the latter, both peptides showed an activity of the same order of magnitude as bradykinin (Rubin, Waugh, Laffan, O'Keefe & Craver, 1963), whilst on guinea-pig blood pressure 6-glycine bradykin has been reported to be even more effective than bradykinin (Erdos, Wohler & Levine, 1963).…”

Copper-Catalyzed Direct Oxidative α-Arylation of Pyrrolidine with Phenols and Naphtols

“…Pyrrolidine-based drugs are also of utmost importance since this scaffold is among the top five most commonly employed nitrogen heterocycles in small molecule drugs. The impact of this heterocycle in human health can easily be evidenced by looking at the structures of major drugs such as Novartis' anti-diabetic vildagliptin 4 [4], Bristol-Myers Squibb's antihypertensive captopril 5 [5] or GSK's anticholinergic procyclidine 6 [6] principally used for the Parkinson's disease and dystonia. Chiral pyrrolidine derivatives are in addition privileged ligands in asymmetric synthesis, *Address correspondence to this author at the Laboratoire de Chimie Organique, Service de Chimie et PhysicoChimie Organiques, Université libre de Bruxelles (ULB), Avenue F.D.…”