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Titolo:
CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI
Autore:
TENBERGE REJ; ROFFEL AF; ZAAGSMA J;
Indirizzi:
UNIV GRONINGEN,DEPT MED CHEM & MOLEC PHARMACOL,GRONINGEN UTRECHT INSTDRUG EXPLORAT 9713 AW GRONINGEN NETHERLANDS
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 2, volume: 352, anno: 1995,
pagine: 173 - 178
SICI:
0028-1298(1995)352:2<173:CIOMMR>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PULMONARY PARASYMPATHETIC NERVES; TRACHEA; PIRENZEPINE; M1; BRONCHOCONSTRICTION; AFFINITY; SUBTYPES;
Keywords:
GUINEA-PIG MAIN BRONCHUS; GANGLIONIC MUSCARINIC M(1) RECEPTORS; VAGAL NERVE STIMULATION; ELECTRICAL FIELD STIMULATION; MUSCARINIC M(1)-RECEPTOR ANTAGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
R.E.J. Tenberge et al., "CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI", Naunyn-Schmiedeberg's archives of pharmacology, 352(2), 1995, pp. 173-178

Abstract

The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field stimulation (EFS, postganglionic)-induced contractions of the guinea-pig main bronchus under various experimental conditions. Using identical stimulation parameters for VNS and EFS (8V, 30 Hz, 0.5 ms, 5s every min), the amplitude of the VNS-induced twitch contractionswas 30.4% of the EFS-induced responses, and pirenzepine showed 2.3-fold selectivity (pIC(50)-values 6.45 and 6.09, respectively) to inhibitvagally induced contractions. With the stimulation frequency for EFS lowered to match contraction levels obtained using VNS, pirenzepine was equipotent to inhibit both types of response at M(1) receptor-selective concentrations, suggesting that M(1) receptors are not involved. By contrast, when the stimulation episode was prolonged until plateau contraction (10-20 s), in the presence of the nicotinic antagonist hexamethonium (5 mu M), the M(2) receptor antagonist AQ-RA 741 (0.1 mu M) and the beta-adrenoceptor antagonist timolol (1 mu M), and again usingmatched VNS- and EFS-induced contraction levels, pirenzepine inhibited nerve stimulation-evoked responses in a biphasic manner, yielding pIC(50)-values of 8.12 (indicative of M(1) receptor blockade) and 6.43 (indicative of M(3) receptor blockade) for the first and second phase, respectively, while postganglionic stimulation showed a purely monophasic inhibition (pIC(50) = 6.32). These results show that facilitatory muscarinic M(1) receptors are involved in vagally mediated contractionof guinea-pig bronchi, under conditions of elevated neurotransmissionand partial nicotinic receptor blockade.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 04:47:15