Detail of "135306-85-3"

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Tachykininergic transmission to the circular muscle of the guinea pig ileum: evidence for the involvement of NK2 receptors

Tachykininergic transmission to the circular muscle of the guinea pig ileum: evidence for the involvement of NK2 receptors. Bartho, Lorand; Santicioli, Paolo; Patacchini, Riccardo; Maggi, Carlo Alberto (Med. Sch., Univ. Pecs, Pecs H-7643, Hung.). Br. J. Pharmacol., 105(4), 805-10 (English) 1992. CODEN: BJPCBM. ISSN: 0007-1188. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors and MEN 10,367 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea pig ileum was investigated. In circular muscle strips of the ileum, elec. field stimulation in the presence of atropine (2 mM) and apamin (0.1 mM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 mM) and MEN 10,376 (3-10 mM) but not by L 659,877 (<10 mM). The presence of apamin was necessary in this exptl. arrangement to unmask an atropine-resistant primary contraction, sensitive to tachykinin antagonists. The motor response was abolished by tetrodotoxin. In circular strips of the ileum GR 71,251 (10 mM) inhibited the tonic contraction produced by [Sar9]substance P sulfone, a selective NK1 receptor agonist but not that produced by [b-Ala8]neurokinin A (4-10), a selective NK2 receptor agonist. 127493-01-0 and 135306-85-3 are cas registry numbers of chemicals which are used as reagents here. By contrast, MEN 10,376 antagonized the effect of the NK2 agonist while leaving the response to the NK1 agonist unaffected. In whole segments of the ileum, distension of the gut wall by an intraluminal balloon placed at ~1 cm from the point of recording of mech. activity of the circular muscle produced atropine-sensitive phase contractions (ascending enteric reflex). In the presence of atropine (2 mM), a noncholinergic response was elicited, which required larger vols. of distension that the cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by apamin (0.1 mM) and abolished by tetrodotoxin, either in the presence or absence of apamin. MEN 10,376 (3-10 mM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 mM each) were ineffective. MEN 10,375 inhibited the atropine-resistant ascending enteric reflex to a larger extent in the absence than in the presence of apamin and also slightly inhibited the ascending enteric reflex in the absence of atropine. These findings provide evidence for an involvement of NK2 tachykinin receptors in excitatory transmission to the circular muscle of the guinea pig ileum. NK2 receptor are also involved in the physiol.-like circular muscle activation produced by stimulation of intramural neuronal pathways which subserve the atropine-resistant ascending enteric reflex. .

Tachykinins and calcitonin gene-related peptide as co-transmitters in local motor responses produced by sensory nerve activation in the guinea pig isolated renal pelvis

Tachykinins and calcitonin gene-related peptide as co-transmitters in local motor responses produced by sensory nerve activation in the guinea pig isolated renal pelvis. Maggi, C. A.; Theodorsson, E.Several substances are used for example 135306-85-3 and 83651-90-5 which are their cas registry numbers.; Santicioli, P.; Giuliani, S. (Pharmacol. Dep., A. Menarini Pharm., Florence 50131, Italy). Neuroscience (Oxford), 46(3), 549-59 (English) 1992. CODEN: NRSCDN. ISSN: 0306-4522. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Elec. field stimulation of circular muscle strips from the guinea pig isolated renal pelvis produces a frequency-dependent pos. inotropic effect of the spontaneous contractions which is unaffected by atropine and guanethidine and abolished by tetrodotoxin or in vitro capsaicin desensitization. Omega conotoxin fraction GVIA inhibited the response to low frequencies of stimulation, but had only a partial or minor inhibitor effect at higher frequencies. Tachykinins produced a concn.-dependent pos. inotropic effect, neurokinin A being more potent than substance P. On the other hand, rat alpha calcitonin gene-related peptide (CGRP) inhibited spontaneous contractions of the renal pelvis. MEN 10376, a neurokinin A(4-10) analog, antagonized and pos. inotropism produced by neurokinin A without affecting the response to KCl, and it suppressed the pos. inotropic response produced by elec. field stimulation. In the presence of MEN 10376, a neg. inotropic response was produced by elec. field stimulation which was antagonized by the C-terminal fragment (8-37) of human alpha calcitonin gene-related peptide (hCGRP). The hCGRP (8-37) antagonized the neg. inotropic effect of exogenously administered CGRP without affecting inhibition by isoprenaline. Application of capsaicin (10 mM) produced a marked increase in the outflow of substance P-, neurokinin A-, and CGRP-like immunoreactivities from the superfused guinea pig renal pelvis. Substance P-, neurokinin A-, and CGRP-like immunoreactivities were also detected in tissue exts. of the renal pelvis by RIA. Thus, peptide release from peripheral endings of capsaicin-sensitive primary afferents represents the major type of nerve-mediated response affecting motility of the guinea pig isolated renal pelvis. Tachykinins and CGRP act as physiol. antagonists, and the excitatory action of tachykinins prevails over the inhibitory action of CGRP. Local modulation of renal pelvis motility by sensory nerves could facilitate removal of irritants present in the urine, protecting the kidney during obstruction and ureteral antiperistalsis. .