title: Beta 2- but not beta 3-adrenoceptors mediate prejunctional inhibition of non-adrenergic non-cholinergic contraction of guinea pig main bronchi.
abstract: We studied the effects of selective beta-adrenoceptor agonists on the cholinergic and non-adrenergic non-cholinergic (excitatory NANC) contractions elicited by electrical field stimulation of guinea pig main bronchi in vitro. Addition of the selective beta 2-adrenoceptor agonists, fenoterol and salbutamol, and the selective beta 3-adrenoceptor agonist, BRL 37344 (4-[2-[(2-hydroxy-2-(3-chlor-phenyl)ethyl)amino]-propyl]-phenoxyac etic acid), induced a dose-dependent inhibition of the cholinergic contraction (pD2 7.89, 6.71 and 4.56, respectively) and the excitatory NANC response (pD2 9.11, 8.16 and 7.42, respectively). Fenoterol- and BRL 37344-induced inhibition of the excitatory NANC response was blocked with high potency (pKB 8.77 and 9.07, respectively) by the selective beta 2-adrenoceptor antagonist, ICI 118,511 (erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamino)-but an-2-ol). A comparable contraction induced by neurokinin A (2 or 5 nM) was also inhibited by fenoterol, salbutamol and BRL 37344, but at significantly higher concentrations than for the inhibition of the excitatory NANC response (pD2 8.72, 7.56 and 6.66, respectively). Such a preferential inhibition of electrical field stimulation- versus agonist-induced effects was not observed for cholinergic contractions (pD2 versus methacholine-induced tone 7.86, 6.93 and 5.10, respectively). The results clearly exclude the involvement of beta 3-adrenoceptors in these responses. Furthermore they show that beta 2-adrenoceptors are involved in the prejunctional inhibition of excitatory NANC contractions, presumably via modulation of tachykinin release from sensory nerves, and solely in the postjunctional inhibition of cholinergic contractions.
authors.affiliation: Groningen/Utrecht Institute for Drug Exploration, Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: Ten Berge
authors.forename: E C
authors.initials: EC
authors.lastname: Weening
authors.forename: A F
authors.initials: AF
authors.lastname: Roffel
authors.forename: J
authors.initials: J
authors.lastname: Zaagsma
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3
chemical_list: D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D005280:Fenoterol; C026777:ICI 118551; C057368:BRL 37344; D015288:Neurokinin A; D000420:Albuterol