Effect of Enkephalin and Substance P on Sympathetic Nerve Transmission in Mouse Vas Deferens

Abstract

Abstract-Effect of methionine-, leucine-enkephalin (met-,leu-enkephalin) and substance P on the transmission in mouse vas deferens was studied. Both met and leu-enkephalin inhibited electrically induced contraction of vas deferens at 10-8-10-7 M, met-enkephalin being 1.4 times more active than leu-enkephalin.Nalorphine (10-6 M) antagonized these effects. Substance P (10-9-10-7 M) had no effect on the contraction.Metand leu-enkephalin (10-7-10-5 M) decreased the high potassium induced [3H]-nor epinephrine release from vas deferens, while substance P (10-5 M) significantly increased it. Nalorphine (10-5 M) reversed the inhibitory effect of met-enkephalin.These results indicate that these peptides modify the transmission of sympathetic nerve in mouse vas deferens.A variety of evidence now indicates that a certain endogenous polypeptide in the central nervous system is involved in the regulation of sensory nerve transmission. Two peptides, methionine and leucine-enkephalin (met and leu-enkephalin) which have been suggested to be endogenous ligands for opiate receptors (1), are localized in synaptosomal fractions (2) and are thought to modulate the activity of the ascending pain pathway in the spinal cord and the brain. Substance P, undecapeptide isolated from bovine hypothalamus (3), is also localized in synaptosomal fractions (4, 5). Since substance P exerts a potent de polarizing action on the motoneurons and is localized for the greater part in the dorsal area of the dorsal horn, the role of an excitatory transmitter of primary afferent neurons was suggested (6).Interestingly, these endogenous polypeptides modulate a stimulus-induced contraction of mouse vas deferens. Thus, both enkephalins depresse the contraction (1) while substance P enhances it (7, 8). In all probability, the depression and the enhancement in contraction reflect a decrease and an increase of transmitter release from sympathetic nerves in the pre paration, respectively. Henderson et al. (9) and Hughes et al. (10) demonstrated that morphine inhibits the transmitter release from mouse vas deferens. Henderson and North (11) and Henderson (12) indirectly suggested that normorphine and met-enkephalin depress the transmitter release from the vas deferens.In planning the present experiments we attempted to confirm the findings that these peptides modulate the contraction of vas deferens and second, to demonstrate the influence

An Electrophysiological Analysis of the Effects of Morphine on the Calcium Dependence of Neuromuscular Transmission in the Mouse Vas Deferens

“…Mg may then displace Ca from the X-sites in the potential-dependent calcium channel, decrease the calcium conductance change which accompanies the nerve impulse and therefore block transmitter release. Morphine, as well as the naturally occurring opiates methionine-enkephalin and leucine-enkephalin (Segawa, Murakami, Ogawa & Yajima, 1978), may also block transmitter release by binding to the X-receptors and displacing Ca ions. This would explain the alteration by opiates of Ca binding to phospholipids in the presynaptic membrane (Mule, 1969) as well as their ability to block transmitter release (Dunlap & Fischbach, 1978).…”

Tachykinins and tachykinin receptors: effects in the genitourinary tract

“…This is also the case for guinea-pig (Sjostrand and Swedin, 1968;von Euler and Hedqvist, 1974;Zetler and Kampmann, 1979;Growcott et al, 1982;Stjernquist et al, 1983;Rovero et al, 1989;Hall and Morton, 1991a,b;Patacchini et al, 1992;Anthes et al, 2002), mouse (Blackwell et al, 1978;Segawa et al, 1978;Parlani et al, 1995) and rabbit (Stjernquist et al, 1983;Maggi et al, 1992a).…”

Postjunctional Localization of Substance P Receptors on the Rat Portal Vein

“…The SP-induced contraction of the guinea pig ileum has been attributed to both a direct action on the smooth muscle and a prejunc tional modulation of acetylcholine release [Hedqvist and von Euler, 1975;Chipkin et al, 1978], although an exclusive action on the smooth muscle has been suggested by Rosell et al [1977], In the case of the mouse vas deferens, conflicting results have been ob tained; on this tissue, the SP myotropic effect is considered to be prejunctional by Segawa et al [1978], or postjunctional by Blackwell et al [1978], Although few studies on postversus prejunctional sites of action of SP on vascular smooth muscle are available, the effects of this peptide on both the rabbit mes-enteric vein [Berube et al, 1978] and the human omental vein [Stjarne, 1980] have been described as postjunctional. The portal vein of the rat has also been shown to be sen sitive to SP [llelle et al, 1980;Hellstrandand Jarhult, 1980], but the mode of action of this peptide on this tissue has not been studied extensively.…”