Neo‐kyotorphin, an analgesic peptide isolated from human lung carcinoma

Abstract

A pentapeptide with analgesic activity has been isolated from human lung squamous cell carcinoma and from three other types of propagated tumors of human lung small-cell carcinoma (SCC), adenoma (AD) and large-cell carcinoma (LCC) in nude mice. The amino acid sequence of the peptide has been revealed to be H-Thr-Ser-Lys-Tyr-Arg-OH, which is exactly the same as that of neo-kyotorphin, an analgesic peptide originally isolated from bovine brain [(1982) Life Sci. 31, 17331. No neo-kyotorphin could be isolated from normal lung tissue using the same procedures as those used for carcinomas. The results suggest that the presence of neo-kyotorphin in the lung carcinoma may represent the ectopic expression of peptide hormone.Our findings constitute the first example of a human lung carcinoma producing analgesic peptide.

A novel system of peptidergic regulation

“…In contrast to neokyotorphin, its fragment induces cytolysis of tumor cells [21, 39]. The presence of high amounts of neokyotorphin in lung carcinoma suggests its involvement in tumor development [40]. It was recently found that two groups of α‐globin fragments, (1–32)‐(1–30) and (106–141)‐(110–141), induce a 30–60% increase of proliferative tumor cell growth [41].…”

“…Accordingly, several pathologies are accompanied by changes in composition and content of the fragments of functional protein in tissues [14–18, 28, 40, 41]. Notwithstanding the clinical and biochemical differences, these pathologies have a common principal feature – they involve alterations in tissue homeostasis or metabolic state of the cells, independently of the nature of the disease: cell transformation [40, 41], tissue atrophy (Alzheimer's disease and ischemia [16–18]) or impaired lymphoproliferation (Hodgkin's disease [28]). Activity of the components of tissue‐specific peptide pools in cell cultures in vitro shows that their biological role might be due to prevention of tumor cell growth or to control of viability, growth and differentiation of cells of the tissues, i.e.…”

GABA-induced changes of the tissue-specific peptide pool of white rat brain

“…However, significant changes in the composition and the content of peptide components of brain were shown to accompany the pathologies associated with alterations of brain metabolism, such as Alzheimer's disease [3] and brain ischemia [8]. Changes in the levels of haemoglobin fragments were detected in human erythrocytes for Hodgkin's disease [9] and lymphosarcoma [10], and in lung tissue during lung carcinoma [11]. Levels of haemoglobin-derived peptides were shown to increase in human blood plasma of donors subjected to physical exercise [12].…”

Proteolytic degradation of hemoglobin by endogenous lysosomal proteases gives rise to bioactive peptides: hemorphins

“…Since the findings of Brantl et al, systematic studies of peptide composition of various tissue extracts resulted in a great number of new peptides with structure mainly originating from α‐ or β‐globin chains [2]. In addition, some of these hemoglobin‐derived peptides were often found to coexist with various pathologies such as human lung adenocarcinoma [4], Alzheimer's disease [5], Hodgkin's disease [6]and brain ischemia [7]and even subsequently to physical exercise like long distance running [8]. In the latter study, it was noteworthy that the plasma level of the released hemorphin‐7 exceeded that of β‐endorphins by a factor of about 1000.…”