Benishin C G, Pearce L B, Cooper J R
J Pharmacol Exp Ther. 1986 Oct;239(1):185-91.
An aqueous extract of brain has recently been shown to contain a factor (substance B) that antagonizes presynaptic inhibition of evoked [3H]acetylcholine release from guinea pig ileal synaptosomes. This factor antagonized the inhibition of electrically evoked contractions of the intact guinea pig longitudinal muscle-myenteric plexus preparation by a variety of pharmacological agents including clonidine, 2-chloroadenosine, morphine and phencyclidine. pA2App values for substance B antagonism of these four agonists were very similar. Schild plot analysis suggests a functional competition between substance B and each of these receptor agonists. In the absence of any agonist, substance B had a minimal effect on the force of contraction. This reversal of inhibition by substance B was not altered by the ganglionic blocking agent hexamethonium. Substance B was not able to reverse the inhibition of contractions elicited by atropine. In addition to its localization in brain, the factor was also found in appreciable quantities in the heart and the ileum, but not in the liver or kidney. These results indicate that an endogenous neuromodulator exists in innervated tissues that antagonizes a subcellular mechanism(s) involved in mediating inhibition of neurotransmitter release by alpha adrenergic, opiate and purinergic agonists, as well as phencyclidine.
最近研究表明，脑水提取物含有一种因子（物质B），该因子可拮抗豚鼠回肠突触体诱发的[3H]乙酰胆碱释放的突触前抑制。该因子可拮抗多种药理剂（包括可乐定、2-氯腺苷、吗啡和苯环利定）对完整豚鼠纵肌-肠肌丛标本电诱发收缩的抑制作用。物质B对这四种激动剂拮抗作用的pA2App值非常相似。Schild图分析表明，物质B与这些受体激动剂之间存在功能竞争。在没有任何激动剂的情况下，物质B对收缩力的影响最小。物质B引起的抑制作用逆转不受神经节阻断剂六甲铵的影响。物质B不能逆转阿托品引起的收缩抑制。除了在脑中定位外，该因子在心脏和回肠中也有相当数量的发现，但在肝脏或肾脏中未发现。这些结果表明，在受神经支配的组织中存在一种内源性神经调节剂，它可拮抗α肾上腺素能、阿片类和嘌呤能激动剂以及苯环利定介导的神经递质释放抑制所涉及的亚细胞机制。
