Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin

Abstract

Mammalian neurokinin A (NKA) and substance P (SP) are neuropeptides widely distributed in the body; they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues. In the present investigation, we studied the age-dependent changes in NKA and SP in ovary, liver, pancreas and spleen as well as the role of exogenous melatonin on these changes. Female rats of 5, 15 or 25 months of age were studied. In the ovary, NKA concentrations did not change during aging. SP concentrations in the control group were significantly higher (P<0.01) in old rats than in the other two age groups studied. Melatonin treatment resulted in reduced concentrations as compared with those of the control old rats. In the pancreas, NKA and SP concentrations increased during aging, the young rats showing significantly lower values (P<0.01) than middle-aged and old rats for NKA and significantly lower (P<0.01) than the old rats for SP. After melatonin treatment the differences in NKA concentrations disappeared and SP decreased in middle-aged as compared with those in old rats. In the liver, NKA and SP concentrations in the control and melatonin-treated groups did not differ significantly for the three age groups studied. Splenic NKA in control and melatonin-treated groups increased from young to middle-age up to old ages. SP concentrations showed similar values at all ages except in melatonin-treated old rats; in these animals there were significantly higher concentrations than in young melatonin-treated rats. The effect of melatonin was mainly observed on the ovary and pancreas in old rats, with a reduction in the concentrations as compared with those observed in the young groups.

Introduction

Mammalian tachykinins (TKs), neurokinin A (NKA), and substance P (SP) are neuropeptides widely distributed in the CNS and other organs. The primary function of these peptides are not completely understood [30]. Through their effects on the vascular tone, they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues [7]. It has been suggested that neurokinins may play an important role in the regulation of autonomic nervous system [34] as well as in modulation of the immune system [37]. SP, among other peptides, may contribute to the local vascular control in the ovary and there may be a relationship between ovulation and vascular endothelial function [44]. Neuropeptides are also particularly important in the coordination of pancreatic exocrine and endocrine secretions. Calcitonin gene-related peptide (CGRP), inmunoreactive neurons and CGRP/SP TKs immunoreactive fibers regulate hepatobiliary activity, including hemodynamic functions of the hepatic vasculature [20]. In addition, binding sites for SP and NKA neuropeptides have been localized in primary afferent nerves which innervate several immune organs including the thymus, spleen, and lymph nodes [16].

Little is known, however, of the developmental pattern of TKs in these organs. Few studies have addressed age-related changes in TKs in non-endocrine tissues, and data on the function and changes in neurokinins during the physiological aging process are limited and the results are conflicting. Reportedly, aging of the CNS has been associated with widespread changes in TK gene expression, suggesting that alterations in tachyninergic system may have implications for the physiopathology of the diseases of the elderly [35].

Aging of the nervous system has not been associated with widespread changes in TK binding but differences in behavioral responses to TK agonists may reflect changes in other transmitter systems which respond to TK input [43]. Finally, in the immunohistochemical study of the brain of young (5 months) versus middle-aged (15 months) and old rats (23–25 months) there was no statistically significant change in neuronal number and size of the neurokinin B and neurokinin-3 receptor staining [27]. The numbers of SP-LI perikarya in the central nervous system of aged hamsters at both day- and night-time were augmented three- to four-fold when compared to adults animals [40]. Recent studies from our laboratory have shown that during aging of the rats, concentrations of TKs in brain areas undergo important alterations, showing increased NKA and SP concentrations in hypothalamus of old rats in comparison to young or middle-aged rats and an opposite developmental pattern in pineal and striatum in which TK concentrations decreased with increasing age [18]. Melatonin treatment restored TK concentrations in hypothalamus of old rats showing values similar to those found in young rats. Striatal or pineal TK concentrations were not modified.

As in blood, levels of melatonin in every other fluid, tissue, and cell thus far studied are higher during the night than during the day [38]. Whereas the 24-h rhythm of melatonin is robust in young animals and humans, the cycle deteriorates during aging and may be totally abolished in neurodegenerative diseases [4], [41]. In the present study we investigated the effects of aging on the concentration of NKA and SP in different body organs. Since melatonin treatment has known [17], [23] to have a beneficial effect in a variety experimental neurodegenerative processes. The indication is that exogenous melatonin may delay the aging process of tissues by means of its free radical scavenging effects [21], [31]. Herein we investigated the possibility that melatonin may also influence TK concentrations in different body organs during aging.