Co-transmission
During the mid-1970s, studies on such invertebrates as the mollusc Aplysia showed that at least four different types of transmitters could be liberated from the same nerve terminal. This was the first evidence that Dale’s Lawdoes not always apply. Extensive histochemical studies of the mammalian peripheral and central nervous systems followed, and it was shown that transmitters such as acetylcholine, noradrenaline and dopamine can coexist with such peptides as cholecystokinin, vasoactive intestinal peptide, and gastrin-like peptides. It is now evident that nerve terminals in the brain may contain different types of storage vesicles that store the peptide co-transmitters. Following their release, these peptides activate specific pre- or postsynaptic receptors, and thereby modulate the responsiveness of the membrane to the action of the traditional neurotransmitters such as acetylcholine or noradrenaline. In the mammalian and human brain, acetylcholine has been found to localize with vasoactive intestinal peptide; dopamine with cholecystokinin-like peptide, and 5-HT with substance P. In addition, there is increasing evidence that some peptides may act as neurotransmitters in their own right in the mammalian brain. These include the enkephalins, thyrotrophinreleasing hormone, angiotensin II, vasopressin, substance P, neurotensin, somatostatin, and corticotropin, among many others. With the advent of specific and sensitive immunocytochemical techniques, several more peptides are being added to this list every year. The peptide transmitters form the largest group of neurotransmitters in the mammalian brain, at least 40 different types having been identified so far. The mechanism governing their release differs from those of the nonpeptide transmitters. Thus peptides are stored in large dense core vesicles which appear to require more prolonged and widespread diffusion of calcium into the nerve terminal before they can be released. In general, the peptide transmitters form part of the slow transmitter group as they activate metabotropic receptors.
During the mid-1970s, studies on such invertebrates as the mollusc Aplysia showed that at least four different types of transmitters could be liberated from the same nerve terminal. This was the first evidence that Dale’s Lawdoes not always apply. Extensive histochemical studies of the mammalian peripheral and central nervous systems followed, and it was shown that transmitters such as acetylcholine, noradrenaline and dopamine can coexist with such peptides as cholecystokinin, vasoactive intestinal peptide, and gastrin-like peptides. It is now evident that nerve terminals in the brain may contain different types of storage vesicles that store the peptide co-transmitters. Following their release, these peptides activate specific pre- or postsynaptic receptors, and thereby modulate the responsiveness of the membrane to the action of the traditional neurotransmitters such as acetylcholine or noradrenaline. In the mammalian and human brain, acetylcholine has been found to localize with vasoactive intestinal peptide; dopamine with cholecystokinin-like peptide, and 5-HT with substance P. In addition, there is increasing evidence that some peptides may act as neurotransmitters in their own right in the mammalian brain. These include the enkephalins, thyrotrophinreleasing hormone, angiotensin II, vasopressin, substance P, neurotensin, somatostatin, and corticotropin, among many others. With the advent of specific and sensitive immunocytochemical techniques, several more peptides are being added to this list every year. The peptide transmitters form the largest group of neurotransmitters in the mammalian brain, at least 40 different types having been identified so far. The mechanism governing their release differs from those of the nonpeptide transmitters. Thus peptides are stored in large dense core vesicles which appear to require more prolonged and widespread diffusion of calcium into the nerve terminal before they can be released. In general, the peptide transmitters form part of the slow transmitter group as they activate metabotropic receptors.
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