A secoisopimarane diterpenoid from Salvia cinnabarina inhibits rat urinary bladder contractility in vitro.
We have evaluated the effect of 3,4-secoisopimar-4(18),7,15-triene-3-oic acid (compound 1), isolated from the aerial parts of Salvia cinnabarina, on the contractile response elicited by electrical field stimulation (EFS) in the rat isolated urinary bladder. Compound 1 (10 ( - 7) - 10 ( - 4) M) produced a concentration-dependent inhibition of the EFS contractile response without modifying the contractions produced by exogenous acetylcholine (10 ( - 6) M). A number of antagonists/inhibitors including a combination of atropine (10 ( - 6) M), phentolamine (10 ( - 6) M), propranolol (10 ( - 6) M) and hexamethonium (10 ( - 4) M), the NK (1) receptor antagonist SR140333 (10 ( - 7) M) plus the NK (2) receptor antagonist SR48968 (10 ( - 6) M), naloxone (10 ( - 6) M), verapamil (10 ( - 7) M), capsazepine (10 ( - 5) M) and the CB (1) receptor antagonist SR141716A (10 ( - 6) M) did not modify the inhibitory effect of compound 1. However, the nitric oxide (NO) synthase inhibitor L-NAME (3 x 10 ( - 4) M), significantly reduced the inhibitory effect of compound 1. It is concluded that compound 1 inhibits rat bladder contractility with a mechanism involving, at least in part, NO production.
Department of Experimental Pharmacology, University of Naples "Federico II", Naples, Italy.
Raffaele
R
Capasso
Angelo A
AA
Izzo
Giovanni
G
Romussi
Francesco
F
Capasso
Nunziatina
N
De Tommasi
Angela
A
Bisio
Nicola
N
Mascolo
D000109:Acetylcholine; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D020128:Inhibitory Concentration 50; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D027544:Salvia; D001743:Urinary Bladder / Q000187:drug effects
D004224:Diterpenes; D010936:Plant Extracts; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester