Variable alpha 2-adrenoceptor-mediated inhibition of bronchoconstriction and peptide release upon activation of pulmonary afferents.
In the present study, we evaluated the possible regulation by alpha 2-receptor agonists (SKF 35886 and UK 14304) of peptide release and functional responses upon sensory nerve activation in the guinea-pig lung. The peptide release and bronchoconstriction caused by antidromic vagal nerve stimulation (low frequency, 1 Hz), and a low concentration of capsaicin (10(-8) M) and resiniferatoxin (3 x 10(-10) M) were attenuated by alpha 2-adrenoceptor agonists. The effects of capsaicin and nicotine in high concentrations and high frequency nerve stimulation (10 Hz) were influenced to a much smaller extent by alpha 2-adrenoceptor stimulation. The calcitonin gene-related peptide release evoked by bradykinin but not the functional effects was inhibited by alpha 2-adrenoceptor activation. It is concluded that alpha 2-adrenoceptor stimulation mainly inhibits the release of mediator and/or the bronchoconstriction caused by moderate activation of sensory nerves. It is necessary to measure mediator release directly to reveal prejunctional effects and not to rely only on indirect functional evidence.
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Y P
YP
Lou
A
A
Franco-Cereceda
J M
JM
Lundberg
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D016084:Bronchoconstriction / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000294:innervation; D015288:Neurokinin A / Q000032:analysis; D009538:Nicotine / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D004224:Diterpenes; D007093:Imidazoles; D010455:Peptides; D011810:Quinoxalines; C035857:xylonidine; D000068438:Brimonidine Tartrate; D009538:Nicotine; D015288:Neurokinin A; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin