1. The effect of arginine vasopressin and its analogs on the synthesis of prostaglandin E2 by rat renal medullary interstitial cells in culture
T R Beck, A Hassid, M J Dunn J Pharmacol Exp Ther. 1980 Oct;215(1):15-9.
Arginine vasopressin (AVP) stimulates renal prostaglandin (PG) production which is thought to inhibit vasopressins' antidiuretic action. Using rat renal medullary cells in culture (RMIC), we compared the ability of the following peptides which possess different biological activities to stimulate prostaglandin biosynthesis: AVP (high antidiuretic and pressor activities); 1-desamino-8-D-arginine vasopressin (a synthetic peptide with high antidiuretic and no pressor activity); and oxytocin (intermediate pressor, low antidiuretic activity). Radiometric thin-layer chromatography of supernatant media from cells incubated with octatritiated or [14C]arachidonic acid revealed only one radiolabeled peak which co-migrated with PGE2. Radioimmunoassay confirmed that PGE2 was the only prostaglandin synthesized by RMIC. Incubation of cells with AVP (1 nM to 3 microM) increased PGE2 synthesis measured by radioimmunoassay in a concentration-dependent fashion up to 2 1/2-fold over control; 1-desamino-8-D-arginine did not increase PGE2 synthesis. Oxytocin stimulated PGE2 synthesis, but was less potent than AVP. Preincubation of RMIC with [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-4-valine, 8-D-arginine]vasopressin, a synthetic nonpressor, nonantidiuretic antagonists of AVP's pressor activity, completely blocked the ability of AVP to stimulate PGE2 synthesis. We conclude that the ability of AVP to stimulate PGE2 synthesis in RMIC is related to its pressor, not its antidiuretic, activity.
2. Relaxant effect of oxytocin on isolated human oviduct
S M Janković, M Varjacić, B Protić Croat Med J. 2001 Oct;42(5):511-6.
Aim: Oxytocin produces concentration-dependent relaxation of isolated isthmus and ampulla of human oviduct precontracted by histamine. The aim of our study was to investigate whether this oxytocin effect was specific and by which receptors it was mediated. Methods: We investigated effects of oxytocin and its antagonists on isolated isthmus and ampulla of the uterine tubes from 20 women who underwent surgery for uterine fibroids. Selective vasopressin and oxytocin antagonists were used to treat isolated preparations of the tubes. Results: In a concentration-dependent manner, oxytocin enhanced spontaneous relaxation of both isthmus (EC50=1.23+/-0.03 x 10(-7) mol/L) and ampulla (EC50=1.04+/-0.26 x 10(-7) mol/L) precontracted by histamine. Neither predominantly selective vasopressin V1 receptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylene-propionyl1,0-metyr2,arg8]-vasopressin (1.0 x 10(-9)-1.0 x 10(-7) mol/L), nor predominantly selective vasopressin V2 antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-D-isoleucine, 4-D-isoleucine]-arginine-vasopressin (1.0 x 10(-9)-1.0 x 10(-7) mol/L) affected significantly the relaxation of isolated ampulla and isthmus produced by oxytocin. On the other hand, [Deamino-Cys1,D-Tyr (Et)2, Thr4, Orn8]-oxytocin, a selective blocker of oxytocin receptors, produced in a concentration-dependent manner (6.7 x 10(-9) mol/L, 2.0 x 10(-8) mol/L, and 6.7 x 10(-7) mol/L) significant shifts of the concentration-response curves of relaxation for oxytocin to the right in isolated preparations of both the ampulla and the isthmus. The values of pA2 for [Deamino-Cys1,D-Tyr (Et)2, Thr4, Orn8]-oxytocin calculated from constrained Schilds plot were 8.08+/-1.53 for ampulla and 7.94+/-0.67 for isthmus. Conclusion: Oxytocin relaxes smooth muscles in human oviduct through a specific effect on oxytocin receptors.
3. Molecular requirements of the active sites of the cholinergic receptors. XIII - Stereospecific synthesis of 3c-methyl-2t-hydroxy-lr-dimethyl-aminomethylcyclopentane methiodide and its dehydroderivative
M Giannella, M Leonelli, M Pigini Farmaco Sci. 1980 Apr;35(4):263-8.
A stereospecific synthesis of 3c-methyl-2t-hydroxy-1r-dimethylaminomethylcyclopentane methiodide (III), which allows better yields, avoiding time-consuming column chromatography and the synthesis of its dehydroderivative (VIII) are described. This last compound, like isomer (VII) (2), shows a good cholinergic activity which, compared with that of the corresponding hydroxycompounds, further supports the dualistic hypothesis of Triggle (8) on the active sites of cholinergic receptors.
