title: Frequency- and train length-dependent variation in the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the field stimulation-induced neurogenic contraction of rat tail artery.
abstract: The present paper examines the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the noradrenaline (NA)-induced neurogenic contractile response to field stimulation mainly with 1-100 pulses at 2 or 20 Hz, in the tail artery of adult normotensive rats. Pharmacological tools were employed to isolate and characterize the alpha 1- and alpha 2-adrenoceptor-mediated components of this response. The degree to which the drugs influenced NA release or reuptake was assessed by their effects on the electrochemically determined, stimulation-induced rise in the NA concentration at the innervated outer surface of the media. This response was unaffected by alpha,beta-methylene ATP (10 microM) or suramin (500 microM), added to desensitize or block P2-purinoceptors, respectively prazosin (0.1 microM) or SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxyl]-3-methyl- 1H-2,3,4,5-tetrohydro-3-benzazepine, 0.1 microM), used to block postjunctional alpha 1- and alpha 2-adrenoceptors respectively, nifedipine (10 microM), blocker of Ca2+ influx through L-type channels, and ryanodine (10 microM), which blocks mobilization of Ca2+ from intracellular stores; it was moderately enhanced by yohimbine (0.1 microM), blocker of pre- and postjunctional alpha 2-adrenoceptors, and strongly enhanced by cocaine (3 microM) or desipramine (1 microM), blockers of NA reuptake. Judging from their inhibitory effects on the contractile responses to the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and xylazine, prazosin (0.1 microM) and SK&F 104078 (0.1 microM) could be used to selectively block alpha 1- and alpha 2-adrenoceptors respectively, while yohimbine (0.1 microM) was less selective, strongly depressing alpha 2- and slightly depressing alpha 1-adrenoceptor-mediated responses. The alpha 1-adrenoceptor-mediated component of the contractile response to short trains at 20 Hz was fast in onset, brief in duration and abolished by ryanodine; that mediated by alpha 2-adrenoceptors was more delayed, prolonged and insensitive to ryanodine. Both components were dose-dependently depressed by nifedipine (0.1-10 microM). The small contractile responses to single pulses, or up to 50 pulses at 2 Hz, or short train (< 4 pulses) at 20 Hz, were more markedly depressed by 0.1 microM yohimbine or SK&F 104078 than by 0.1 microM prazosin and, hence, mediated mainly by alpha 2-adrenoceptors. The reverse was true of the much larger response to longer trains at 20 Hz, which thus probably was mediated mainly by alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology I, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J X
authors.initials: JX
authors.lastname: Bao
authors.forename: F
authors.initials: F
authors.lastname: Gonon
authors.forename: L
authors.initials: L
authors.lastname: Stjärne
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D004563:Electrochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013623:Tail / Q000098:blood supply
chemical_list: D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D058914:Purinergic Antagonists; D011942:Receptors, Adrenergic, alpha; D002118:Calcium; D009638:Norepinephrine