β 2 -Adrenoceptor Regulation of CGRP Release from Capsaicin-sensitive Neurons

Abstract

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 β-adrenoceptors. We evaluated the hypothesis that activation of β-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 β₂-adrenoceptor antagonist, ICI 118,551, but not by pre-treatment with the selective β₁-adrenoceptor antagonist, atenolol. In addition, application of albuterol, a selective β₂-adrenoceptor agonist, significantly blocked capsaicin-evoked release of iCGRP. Collectively, these studies demonstrate that activation of β₂-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, β₂-adrenoceptor agonists may have clinical utility as peripherally acting therapeutics for dental pain and inflammation.

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