beta 2-Adrenoceptor regulation of CGRP release from capsaicin-sensitive neurons.
Previous studies have suggested that neurotransmitter substances from the sympatho-adrenomedullary system regulate pulpal blood flow (PBF), in part, by the inhibition of vasoactive neuropeptide release from pulpal sensory neurons. However, no study has evaluated the role of beta-adrenoceptors. We evaluated the hypothesis that activation of beta-adrenoceptors inhibits immunoreactive calcitonin gene-related peptide (iCGRP) release from capsaicin-sensitive nociceptive neurons via in vitro superfusion of bovine dental pulp. Either norepinephrine or epinephrine inhibited capsaicin-evoked iCGRP. The norepinephrine effect was blocked by the selective beta(2)-adrenoceptor antagonist, ICI 118,551, but not by pre-treatment with the selective beta(1)-adrenoceptor antagonist, atenolol. In addition, application of albuterol, a selective beta(2)-adrenoceptor agonist, significantly blocked capsaicin-evoked release of iCGRP. Collectively, these studies demonstrate that activation of beta(2)-adrenoceptors in dental pulp significantly reduces exocytosis of neuropeptides from capsaicin-sensitive nociceptors. This effect may have physiologic significance in regulating PBF. Moreover, since capsaicin selectively activates nociceptors, beta(2)-adrenoceptor agonists may have clinical utility as peripherally acting therapeutics for dental pain and inflammation.
Bowles
W R
WR
Division of Endodontics, University of Minnesota School of Dentistry, USA.
Flores
C M
CM
Jackson
D L
DL
Hargreaves
K M
KM
D018663:Adrenergic Agents / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002417:Cattle; D003782:Dental Pulp / Q000294:innervation*; D004837:Epinephrine / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005260:Female; D007509:Irritants / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D058666:Adrenergic beta-2 Receptor Agonists; D007509:Irritants; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; D001262:Atenolol; D015740:Calcitonin Gene-Related Peptide; D000420:Albuterol; D002211:Capsaicin; D009638:Norepinephrine; D004837:Epinephrine