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- Title
Pharmacological characterization of muscarinic receptor subtypes mediating vasoconstriction of human umbilical vein.
- Authors
Pujol Lereis, Virginia Andrea; Hita, Francisco Javier; Gobbi, Mauro Darío; Verdi, Marcela Gomez; Rodriguez, María Cecilia; Rothlin, Rodolfo Pedro; Gobbi, Mauro Darío; Rodriguez, María Cecilia
- Abstract
The present study attempted to pharmacologically characterize the muscarinic receptor subtypes mediating contraction of human umbilical vein (HUV).HUV rings were mounted in organ baths and concentration–response curves were constructed for acetylcholine (ACh) (pEC50: 6.16±0.04; maximum response 80.00±1.98% of the responses induced by serotonin 10 μM). The absence of endothelium did not modify the contractile responses of ACh in this tissue.The role of cholinesterases was evaluated: neither neostigmine (acetylcholinesterase inhibitor) nor iso-OMPA (butyrylcholinesterase inhibitor) modified ACh responses. When both enzymes were simultaneously inhibited, a significantly but little potentiation was observed (control: pEC50 6.33±0.03; double inhibition: pEC50 6.57±0.05).Atropine, nonselective muscarinic receptors antagonist, inhibited ACh-induced contraction (pKB 9.67). The muscarinic receptors antagonists pirenzepine (M1), methoctramine (M2) and pFHHSiD (M3) also antagonized responses to ACh. The affinity values estimated for these antagonists against responses evoked by ACh were 7.58, 6.78 and 7.94, respectively. On the other hand, PD 102807 (M4 selective muscarinic receptors antagonist) was ineffective against ACh-induced contraction.In presence of a blocking concentration of pirenzepine, pFHHSiFD produced an additional antagonism activity on ACh-induced responses.The M1 muscarinic receptors agonist McN-A-343 produced similar maximum but less potent responses than ACh in HUV. The calculated pA2 for pirenzepine against McN-A-343 induced responses was 8.54.In conclusion, the data obtained in this study demonstrate the role of M1 muscarinic receptor subtypes and suggest the involvement of M3 muscarinic receptor subtypes in ACh-induced vasoconstriction in HUV rings. In addition, the vasomotor activity evoked by ACh does not seem to be modulated by endothelial factors, and their enzymatic degradation appears to have little functional relevance in this tissue.British Journal of Pharmacology (2006) 147, 516–523. doi:10.1038/sj.bjp.0706654; published on line 30 January 2006
- Subjects
PHARMACOLOGY; ACETYLCHOLINE; CHOLINESTERASES; BUTYRYLCHOLINESTERASE; SEROTONIN; MEDICAL sciences; VASOMOTOR system; AMINES; ATROPINE; BENZODIAZEPINES; CELL receptors; COMPARATIVE studies; ENZYME inhibitors; RESEARCH methodology; MEDICAL cooperation; PIPERIDINE; RESEARCH; TRANQUILIZING drugs; EVALUATION research; VASOCONSTRICTION; IN vitro studies; UMBILICAL veins; PHARMACODYNAMICS; PHYSIOLOGY; CELL physiology
- Publication
British Journal of Pharmacology, 2006, Vol 147, Issue 5, p516
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0706654