The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons.
The anti-inflammatory effect (AI) induced by peripheral injection of diluted bee venom (dBV) involves activation of spinal cord circuits and is mediated by catecholamine release from adrenal medulla, but the precise neuronal mechanisms involved are not fully understood. In a recent study, we demonstrated that an increase in spinal acetylcholine is involved in mediating the anti-inflammatory effect of dBV and that this mediation also involves adrenomedullary activation. The present study utilized the mouse air pouch inflammation model to evaluate the involvement of spinal acetylcholine receptors and sympathetic preganglionic neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT) pretreatment with atropine (muscarinic cholinergic antagonist) but not hexamethonium (nicotinic cholinergic antagonist) significantly suppressed dBVAI on zymosan-evoked leukocyte migration. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic receptor type 2; M(2) antagonist), but not pirenzepine (an M(1) antagonist) or 4-DAMP (an M(3) antagonist), suppressed the dBVAI. In addition, dBV stimulation specifically increased Fos expression in SPNs of the T7-T11, but not the T1-T6 or T12-L2 spinal cord segments, in animals with zymosan-induced inflammation. Moreover, IT methoctramine pretreatment suppressed this dBV-induced Fos expression specifically in SPNs of T7-T11 level. Peripheral sympathetic denervation using 6-hydroxydopamine (6-OHDA) treatment (which spares sympathetic adrenal medullary innervation) did not alter dBVAI. Collectively these results indicate that dBV stimulation leads to spinal cord acetylcholine release that in turn acts on spinal M(2) receptors, which via a hypothesized disinhibition mechanism activates SPNs that project to the adrenal medulla. This activation ultimately leads to the release of adrenal catecholamines that contribute to dBVAI.
Yoon
Seo-Yeon
SY
Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea.
Kim
Hyun-Woo
HW
Roh
Dae-Hyun
DH
Kwon
Young-Bae
YB
Jeong
Tae-Oh
TO
Han
Ho-Jae
HJ
Lee
Hye-Jung
HJ
Choi
Sun-Mi
SM
Ryu
Yeon-Hee
YH
Beitz
Alvin J
AJ
Lee
Jang-Hern
JH
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001285:Atropine / Q000494:pharmacology; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects / Q000378:metabolism; D001514:Bee Venoms / Q000008:administration & dosage*; D002395:Catecholamines / Q000378:metabolism; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013563:Sympathectomy, Chemical / Q000379:methods
D000893:Anti-Inflammatory Agents; D001514:Bee Venoms; D002395:Catecholamines; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D016761:Oncogene Proteins v-fos; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D018738:Hexamethonium; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D016627:Oxidopamine; D002795:Choline O-Acetyltransferase