After binding to the specific neurokinin-1 (NK-1) receptor, the peptide substance P (SP), which is widely distributed in both the central and peripheral nervous systems, induces tumor cell proliferation, angiogenesis, and migration of the tumor cells for invasion and metastasis. However, after binding to NK-1 receptors, NK-1 receptor antagonists inhibit the three above mechanisms. In fact, the antiproliferative action exerted by NK-1 receptor antagonists is because they induce cancer cells to die by apoptosis, whereas SP exerts an antiapoptotic effect. Moreover, it is known that NK-1 receptors are overexpressed in tumors and that tumor cells express several isoforms of the NK-1 receptor. All these data suggest that the SP/NK-1 receptor system could play an important role in the development of cancer; that SP may be a universal mitogen in NK-1 receptor-expressing tumor cells, and that NK-1 receptor antagonists could offer a promising therapeutic strategy for the treatment of human cancer, since they act as broad-spectrum antitumor agents. In sum, the NK-1 receptor may be a new and promising target in the treatment of human cancer.

This study showed that the same isoforms of the neurokinin-1 receptor are present in human retinoblastoma cell lines WERI-Rb-1 and Y-79. Both L-732,138 and L-733,060 can induce apoptosis in these cell lines and therefore can act as antitumoral agents. Primary retinoblastoma specimens display neurokinin-1 receptor immunolabeling. These results suggest that the neurokinin-1 receptor may be a promising new target for the treatment of retinoblastoma.

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Several cholinergic regions have been detected in the brainstem of mammals. In general, these regions are constant among different species, and the nuclear complement is maintained in animals belonging to the same order. The cholinergic system of the brainstem has been partially described in Cetartiodactyla, except for the medulla oblongata. In this work carried out in the alpaca, the description of the cholinergic regions in this order is completed by the immunohistochemical detection of the enzyme choline acetyltransferase (ChAT). In addition, using double immunostaining techniques, the relationship between the cholinergic system and the distribution of calcitonin gene-related peptide (CGRP) previously described is analysed. Although these two substances are found in several brainstem regions, the coexistence in the same cell bodies was observed only in the laterodorsal tegmental nucleus, the nucleus ambiguus and the reticular formation. These results suggest that the interaction between ChAT and CGRP may be important in the regulation of voluntary movements, the control of rapid eye movement sleep and states of wakefulness as well as in reward mechanisms. Comparing the present results with others previously obtained by our group regarding the catecholaminergic system in the alpaca brainstem, it seems that CGRP may be more functionally related to the latter system than to the cholinergic system.