title: The competitive antagonistic effect of compounds from Mandevilla velutina on kinin-induced contractions of rat uterus and guinea-pig ileum in vitro.
abstract: 1. Pure non-peptide compounds obtained in crystal form from the crude extract of the plant Mandevilla velutina (Apocynaceae) were analysed for their antagonistic effects on rat uterine and guinea-pig smooth muscle contractions induced by bradykinin (Bk), lisyl-bradykinin (L-Bk), acetylcholine (ACh), oxytocin and histamine, in vitro. 2. Pre-incubation of rat uterine muscle with compounds MV 8608, MV 8609, MV 8610, MV 8611 and MV 8612 (5 to 40 micrograms ml-1) caused parallel and concentration-dependent rightward displacements of the Bk concentration-response curves (1 to 1000 nM). Schild plots of these data were linear (correlation close to 1) and yielded nominal pA2 values (g ml-1) of 5.7, 5.6, 5.4, 5.7 and 5.3, respectively. Compounds MV 8608, MV 8611 and MV 8612 (5 to 20 micrograms ml-1) also caused concentration-dependent and parallel displacements to the right of the concentration-response curve to L-Bk (1 to 10,000 nM). The Schild plots were linear and furnished nominal pA2 values (g ml-1) of 5.4, 5.8 and 5.1, respectively. With the exception of the antagonist effect of compound MV 8606 against Bk-induced contraction, all compounds behaved as simple competitive kinin antagonists since the calculated slopes were not different from unity. 3. In the guinea-pig ileum, both MV 8608 and MV 8612 (5 to 20 micrograms ml-1), produced concentration-dependent rightward displacements of the concentration-response curve to Bk (0.1 to 1000 nM) when the experiments were performed in the presence but not in the absence of atropine (2.5 microM). However, in contrast to the result obtained in the rat uterus, compound MV 8608 also caused a significant reduction of the maximal response to Bk. The Schild plot for compound MV 8612 was linear (correlation close to unity) and furnished a nominal pA2 value (g ml-1) of 5.3 and a slope not different from unity. 4. In rat uterine muscle, compounds MV 8608 and MV 8612 at concentrations producing marked rightward displacements of the kinin concentration-response curves (10 and 20 micrograms ml-1), did not influence the uterine contractile response to oxytocin or ACh, indicating some selectivity towards kinin receptors. Similarly, compound MV 8612 (10 and 20 ygml 1) did not interfere with the sensitivities or the maximal responses to ACh and histamine in the guinea-pig ileum, whereas compound MV 8608 (10 and 20ug ml-1) caused a slight reduction of ACh- and histamine-induced maximal contractions, allied to decrease of the sensitivity to histamine at concentrations of 20pgml-1 or more. 5. These results extend our previous data, indicating the existence of several non-peptide compounds in the crude extract of Mandevilla velutina that act as simple, competitive, selective and reversible kinin receptor antagonists in the rat isolated uterus and guinea-pig ileum smooth muscle.
authors.affiliation: Department of Pharmacology CCB, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
authors.forename: M G
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: R A
authors.initials: RA
authors.lastname: Yunes
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D007705:Kinins; D010121:Oxytocin; D000109:Acetylcholine; D001920:Bradykinin