1ATP, 2-chloro-ATP, 2-methylthio-ATP, and their unnatural L-enantiomers, were synthesized and their effects tested on the guinea-pig taenia coli and urinary bladder, and the stimulated frog ventricle. 2 The potent P2-purinoceptor agonists, 2-chloro-ATP and 2-methylthio-ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea-pig taenia, but approximately as effective as ATP in contracting the guinea-pig bladder and augmenting the force of contraction of the frog ventricle. 3 A high degree of stereoselectivity was observed for relaxations of the guinea-pig taenia coli produced by theP2-purinoceptoragonists, and 2-methylthio-ATP was over 700 times more effective than its L-enantiomer. In contrast, stereoselectivity for contraction of the guinea-pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle. 4 These results show that P2-purinoceptors mediating inhibitory responses in the guinea-pig taenia coli can show a high degree of stereoselectivity, while P2-purinoceptors mediating excitatory responses in the guinea-pig bladder and in the frog ventricle show little stereoselectivity. 5 The partial stereoselectivity of the P2-purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P, -purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.
Application of a highly specific antiserum against GABA to whole-mount preparations of the guinea pig and rat myenteric plexus resulted in discrete and unambiguous immunolabeling of a subpopulation of myenteric neuronal cell bodies and fibers. The anti-GABA antiserum, which was raised against GABA conjugated by glutaraldehyde to BSA, was applied to glutaraldehyde-fixed whole mounts and subsequently visualized using the peroxidase-antiperoxidase method. In the guinea pig ileum and colon, immunoreactive varicose nerve fibers and scattered nerve cell bodies were found within the myenteric plexus. Immunostained fibers were also seen in the tertiary plexus and in the circular muscle, running parallel to the muscle bundles. GABA immunoreactivity in these intramuscular nerves was most pronounced in the colon. In the rat, immunoreactive fibers were prominent throughout the myenteric plexus. They formed dense networks within the myenteric ganglia, which also contained immunopositive nerve cell bodies, and ran between them in the interconnecting nerves. Some immunoreactive nerve fibers were seen in the circular muscle. Control experiments using non-immune sera or adsorbed anti-GABA antiserum showed no staining. These results add a definitive support to our previous suggestion that GABA serves as an autonomic neurotransmitter in vertebrates. In addition to the present immunohistochemical evidence, this hypothesis is supported by biochemical, autoradiographic, transmitter release, electrophysiological, and pharmacological studies on the enteric nervous system of several species. It is now important to determine the functional role of GABAergic neurons within the complex neuronal circuitry that controls gut functions.
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