Effects Of Tachykinins On Uterine Smooth Muscle

Abstract

1. Sensory nerves supplying the mammalian uterus have been shown to contain substance P (SP) and neurokinin (NK)A. This review presents some of the advances that have led to a greater understanding of the effects of tachykinins on uterine smooth muscle. 2. The cell-surface peptidase neprilysin (EC.3 24.11, endopeptidase 24.11, enkephalinase, CALLA, CD10) has been shown to play a major role in regulating the actions of tachykinins on both rat and human myometrium. Because this peptidase is known to be regulated by steroids and pregnancy, its effects may be of physiological relevance. 3. Tachykinins produce contractions of isolated myometrial preparations from non-pregnant rats and mice. The NK2 receptor mediates these effects in rat uterus, while the NK1 receptor may mediate these effects in the mouse uterus. 4. The effects of tachykinins have been examined on myometrial preparations obtained at Caesarean section from near-term pregnant women. In the presence of the peptidase inhibitors (thiorphan, captopril and bestatin), the mammalian tachykinins SP, NKA and NKB produced concentration-dependent uterine contractions. 5. The order of agonist potency NKA > SP = NKB suggested that NK2 receptors mediate uterine contractions in the human. This was confirmed using the stable analogues [Sar9,Met(O2)11]SP, [Lys5MeLeu9Nle10]NKA(4-10) and [N-MePhe7]NKB, which are NK1, NK2 and NK3 receptor selective, respectively. Only [Lys5MeLeu9Nle10]NKA(4-10) produced concentration-related contractions of human uterine smooth muscle. 6. The experimental findings described in the present review, taken together with results published previously in the literature, indicate that tachykinin peptides may play a physiological or pathophysiological role in regulating uterine smooth muscle activity. However, more extensive research will be required to confirm such a role for these peptides.

Tachykinins and tachykinin receptors: a growing family

“…For many years, the tachykinins were considered almost exclusively as peptides of neuronal origin. NKB is present in the central nervous system and the spinal cord (Kangawa et al, 1983;Moussaoui et al, 1992;Goubillon et al, 2000;Patacchini et al, 2000) while SP and NKA are found in the central nervous system and also in primary afferent sensory neurons supplying a number of peripheral tissues (Holzer, 1988;Maggi and Meli, 1988;Lundberg, 1996;Patak et al, 2000a). SP and NKA are released from nerve endings at both the spinal cord and the peripheral level and play a role as excitatory neurotransmitters (Lembeck and Holzer, 1979;Maggi, 1991;Otsuka and Yoshioka, 1993;Meini and Maggi, 1994;Patacchini et al, 1998, Patak et al, 2000a.…”

Coordination abilities of neurokinin A and its derivative and products of metal-catalyzed oxidation

“…For many years, the tachykinins were considered almost exclusively as peptides of neuronal origin. SP and NKA are found in the central nervous supplying a number of peripheral tissues [1,2]. SP and NKA are released from nerve ending at both the spinal cord and the peripheral level and play a role as excitatory neurotransmitters [2,3].…”

Tachykinins and tachykinin receptors in human uterus

“…To date, the majority of molecular (Pinto et al, 1999;Candenas et al, 2001), immunohistochemical (Traurig et al, 1984;Papka et al, 1985) and functional (Fisher et al, 1993;Pennefather et al, 1993b;Fisher & Pennefather, 1997;Magraner et al, 1998;Patak et al, 2000a) studies of the uterine distribution of tachykinins, tachykinin receptors and/or degradation of tachykinins have been conducted using the rat. It is now emerging, however, that there are species (Patak et al, 2000a, b;2002a) as well as hormonal-and pregnancyrelated differences in tachykinin expression and actions in the mammalian myometrium (Pinto et al, 1999;Candenas et al, 2001).…”