Neuropeptide-induced contraction and relaxation of the mouse anococcygeus muscle.

Abstract

Isometric tension responses to neuropeptides were recorded from anococcygeus muscles isolated from male mice. This smooth muscle tissue is innervated by inhibitory nonadrenergic, noncholinergic nerves that resemble, ultrastructurally, the peptidergic neurons of the gastrointestinal tract; the physiological function of the anococcygeus is not known. Slow sustained contractions were produced by oxytocin (0.2-20 nM), , and [Arg]-vasotocin (0.4-100 nM); the mouse anococcygeus is, therefore, one of the few examples of nonvascular smooth muscle from male mammals to respond to low concentrations of oxytocin and related peptides. Substance P (0.5-8 ,AM) caused distinctive, biphasic increases in muscle tone of some, but not all, preparations. Other neuropeptides producing contractions were neurotensin (2-100 ,uM) and thyrotropin-releasing hormone (2-100 ,AM); the responses were of similar time course and displayed selective cross-desensitization, suggesting that these two peptides act through a common distinct mechanism. Tetradecapeptide somatostatin (10-80 pM) and its analog urotensin 11 (0.1-5 ,uM), a dodecapeptide from the urophysis of the teleost fish Gilichthys mirabilis, produced similar slowly developing relaxations of carbachol-induced tone. Piscine urotensin II, of which there are no reported effects on nonvascular mammalian systems, was 20-50 times more potent than somatostatin, a well-established mammalian hormone. Of the peptides studied, only vasoactive intestinal polypeptide (0.05-1 ,uM) caused rapid powerful relaxations in low concentrations; this is consistent with its proposed involvement in nonadrenergic, noncholinergic neurotransmission in the mouse anococcygeus.The anococcygeus muscles are two thin sheets of smooth muscle that arise, separately, from tendonous origins on the posterior sacral vertebrae and run caudad around both sides of the rectum to unite on its ventral aspect; a physiological function of the tissue has yet to be elucidated (1). The muscles of all species studied to date (rat, cat, rabbit, dog, mouse, and ox) are innervated by motor sympathetic fibers, of which the transmitter is norepinephrine, and by inhibitory nonadrenergic, noncholinergic (NANC) fibers, of which the transmitter is unidentified (1-6). Ultrastructurally, the NANC nerves of the anococcygeus resemble the p-type fibers of the gastrointestinal tract, suggesting that the transmitter may be a peptide (7). It has been proposed recently that vasoactive intestinal polypeptide (VIP) might be involved in NANC transmission in the mouse anococcygeus (8). However, NANC relaxations of the mouse anococcygeus in response to field stimulation are complex, and it is possible that there is more than one NANC transmitter in this tissue (9). Consequently, we have investigated the effects of a wide range of neuropeptides on tone of the mouse anococcygeus in vitro. The anococcygeus muscle is unusually sensitive to substances that act by releasing norepinephrine from sympathetic nerve endings (1). To prevent such effects, each pre...

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

“…In agreement with these data, it has previously been reported that UII inhibits carbachol-induced contraction of the anococcygeous muscle (44) and that dbcAMP and forskolin counteract the contractile response evoked by UII in rat aortic strips (45). UII has also been shown to lower cytoplasmic free Ca 2þ concentration in goby enterocytes (46).…”

Differential vasoconstrictor activity of human urotensin‐II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey

“…However, as discussed below, such a hypothesis is not supported by radioligand binding or functional studies performed in both native tissue and recombinant rat/human GPR14 cell lines e.g. non-murine U-II isopeptides are active in mouse non-vascular tissue (goby U-II in the mouse anococcygeus; Gibson et al, 1984), mouse U-II contracts rat aortae and functions as a high a nity ligand at both rat and human GPR14 (Douglas & Aiyar, unpublished observations).…”

“…However, as discussed below, such a hypothesis is not supported by radioligand binding or functional studies performed in both native tissue and recombinant rat/human GPR14 cell lines e.g. non-murine U-II isopeptides are active in mouse non-vascular tissue (goby U-II in the mouse anococcygeus; Gibson et al, 1984), mouse U-II contracts rat aortae and functions as a high a nity ligand at both rat and human GPR14 (Douglas & Aiyar, unpublished observations).To illustrate further the di erences in reactivity between species, U-II was found to exhibit a`coronary-selective' vasoconstrictor pro®le in the dog. This contrasted the vasoconstrictor pro®le of human U-II in the pig where, once again, the spasmogenic pro®le was unique to this species.…”

Complex effects of Gillichthys urotensin II on rat aortic strips

“…However, early experiments were carried out with partially purified UII from extracts of fish urophysis; more recently, clear biological activity in mammals has been obtained with a synthetic UII (GUII), having the amino acid sequence of the peptide found in the long-jawed mudsucker, Gillichthys mirabilis (Pearson et al, 1980). An initial observation that GUII produced doserelated relaxations of the mouse anococcygeus muscle (Gibson et al, 1984) prompted further studies of possible actions in mammalian species. In anaesthetized rats, GUII both increased arterial pulse pressure and lowered mean arterial blood pressure (Gibson et al, 1986).…”