Stimulant action of pituitary adenylate cyclase-activating peptide on normal and drug-compromised peristalsis in the guinea-pig intestine.
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1. Pituitary adenylate cyclase-activating peptide (PACAP) is known to influence the activity of intestinal smooth muscle. This study set out to examine the action of PACAP on normal and drug-inhibited peristalsis and to shed light on its site and mode of action. 2. Peristalsis in isolated segments of the guinea-pig small intestine was elicited by distension through a rise of the intraluminal pressure. Drug-induced motility changes were quantified by alterations of the peristaltic pressure threshold at which aborally moving peristaltic contractions were triggered. 3. PACAP (1-30 nM) stimulated normal peristalsis as deduced from a concentration-related decrease in the peristaltic pressure threshold (maximum decrease by 55%). The peptide's stimulant effect remained intact in segments pre-exposed to apamin (0.5 microM), N-nitro-L-arginine methyl ester (300 microM), naloxone (0.5 microM), atropine (1 microM) plus naloxone (0.5 microM) or hexamethonium (100 microM) plus naloxone (0.5 microM). 4. PACAP (10 nM) restored peristalsis blocked by morphine (10 microM), noradrenaline (1 microM) or N6-cyclopentyladenosine (0.3 microM) and partially reinstated peristalsis blocked by Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine (100 microM) but failed to revive peristalsis blocked by hexamethonium (100 microM) or atropine (1 microM). The peptide's spectrum of properistaltic activity differed from that of naloxone (0.5 microM) and forskolin (0.3 microM). 5. The distension-induced ascending reflex contraction of the circular muscle was facilitated by PACAP (1-30 nM) which itself evoked transient nerve-mediated contractions of intestinal segment preparations. 6. These data show that PACAP stimulates normal peristalsis and counteracts drug-induced peristaltic arrest by a stimulant action on excitatory enteric motor pathways, presumably at the intrinsic sensory neurone level. The action of PACAP seems to involve multiple signalling mechanisms including stimulation of adenylate cyclase. (+info)
The deep tendon and the abdominal reflexes.
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The deep tendon reflexes (and the abdominal reflexes) are important physical signs which have a special place in neurological diagnosis, particularly in early disease when they alone may be abnormal. They act as "hard" signs in situations where clinical assessment is complicated by patient anxiety, and become more useful as clinical experience develops. (+info)
Antinociceptive effects of N-acyloctahydropyrido[3,2,1-ij][1,6]naphthyridine in mice: structure-activity relation study of matrine-type alkaloids part II.
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N-Acyloctahydropyrido[3,2,1-ij][1,6]naphthyridines were synthesized as derivatives of matrine-type alkaloids, and the structure-activity relations were examined by the acetic acid-induced abdominal contraction test. The antinociceptive potencies of N-acyloctahydropyrido[3,2,1-ij][1,6]naphthyridines were significantly lower than those of (+)-matrine. The antinociceptive effects of N-benzyloctahydropyrido[3,2,1-ij][1,6]naphthyridines are approximately 5.6 to 6.5 times less than those of N-benzoyloctahydropyrido[3,2,1-ij][1,6]naphthyridine. These findings suggest that the amide group of matrine-type alkaloids is an essential functional group that influences antinociceptive potency. The antinociceptive effect of 4c was markedly antagonized by pretreatment with Naloxone, and that of 3c partially so. (+info)
Visceromotor and spinal neuronal responses to colorectal distension in rats with aldosterone onto the amygdala.
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Stereotaxic delivery of corticosterone onto the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. Since corticosterone activates both the mineralocorticoid (MR) and glucocorticoid (GR) receptors, the aim of this study was to determine the importance of MRs in the regulation of colorectal hypersensitivity through the use of aldosterone that preferentially binds to MRs. Fischer-344 rats received either aldosterone (n = 18)- or cholesterol (control, n = 18)-containing micropellets bilaterally placed stereotaxically on the dorsal margin of the amygdala. After 1 wk, colorectal sensitivity to distension (30 mmHg) was measured in a subgroup of rats (n = 8/group). In other rats (n = 10/group), extracellular potentials of single L6-S1 spinal neurons in response to colorectal distension (CRD; 10-80 mmHg) were recorded. In aldosterone-implanted rats, CRD produced a greater visceromotor behavioral response compared with cholesterol controls (19 +/- 0.5 vs. 11.5 +/- 2.7; P < 0.01). A total of 68/182 (37%) and 56/167 (34%) of spinal neurons responded to noxious CRD in aldosterone-implanted and control groups, respectively. A total of 36/42 (86%) neurons excited by CRD had spontaneous activity in aldosterone-implanted groups compared with control (19/33, 58%, P < 0.01). Neurons with low thresholds for excitatory responses to CRD were seen more frequently in aldosterone-implanted rats than those in the control group (35/39 vs. 18/31, P < 0.05). Maximal excitatory responses of neurons to CRD in aldosterone-implanted rats were significantly greater (23.9 +/- 2.2 vs. 16.4 +/- 2.0 imp/s, P < 0.05), and the durations were longer (34.3 +/- 2.7 vs. 24.9 +/- 1.4 s, P < 0.05) than those in control group. Finally, a greater number of neurons had wide dynamic range responses to somatic stimulation in aldosterone-treated rats compared with cholesterol controls. Our findings suggest that, in the amygdala, MR receptor-mediated mechanisms are likely involved in descending pathways onto lumbosacral spinal neurons that induce colorectal hypersensitivity to luminal distension. (+info)
Haemodynamic and abdominal motor reflexes elicited by neurotensin in anaesthetized guinea-pigs.
(5/20)
1. Single intraperitoneal (i.p.) injections of neurotensin (NT) (0.14- 140 nmol kg-1) in anaesthetized guinea-pigs were found to trigger transient abdominal wall contractions (TAWC) accompanied by relatively sustained increases of systemic blood pressure (BP) and heart rate (HR). The modification of the latter NT effects by various drugs and surgical manipulations was examined to obtain some insight into the nature of, and possible relationship between, these responses. 2. The abdominal motor response (i.e. TAWC) to i.p. NT (14 nmol kg-1) was inhibited by prior i.v. injection of the guinea-pigs with pancuronium (0.27 mumol kg-1), morphine (1.5 and 15 mumol kg-1), clonidine (0.34 mumol kg-1), by concomitant i.p. injection of procaine 2% w/v, or by acute spinalization. It was potentiated by naloxone (2.8 and 28 mumol kg-1), but not affected by i.v. injection of autonomic drugs (i.e. pentolinium, prazosin, yohimbine and atropine), by capsaicin desensitization, or by acute bilateral cervical vagotomy. In spinalized animals a sustained abdominal wall contraction (SAWC) was unmasked, which was resistant to i.v. morphine, clonidine or baclofen but suppressed by i.v. pancuronium or i.p. lignocaine 2% w/v. 3. Haemodynamic responses to i.p. NT were not affected by i.v. pancuronium, morphine, naloxone, atropine, or by vagotomy. They were inhibited by i.v. pentolinium or clonidine (BP, HR), i.v. prazosin (BP), i.p. procaine 2% w/v (BP, HR), capsaicin desensitization or acute spinalization (BP, HR). Yohimbine (i.v.) potentiated BP and HR increases caused by i.p. NT.4. These results suggest that: (1) the haemodynamic and TAWC responses to i.p. NT in this animal model, are two independent, neurally-mediated reflexes which are likely to originate from the abdominal cavity and require a functionally intact spinal cord for their full expression; (2) the neural pathways subserving both types of responses appear to be different from each other. The nature and time-response characteristics of the reflexes caused by i.p. NT, raise the possibility that i.p. NT is a noxious stimulus, at least in guinea-pigs. (+info)
Ultrasound evaluation of dynamic responses of female pelvic floor muscles.
(6/20)
Ultrasound imaging of the pelvic floor carries diagnostically important information about the dynamic response of the pelvic floor muscles (PFM) to potentially incontinence-producing stress, which cannot be readily captured and assimilated by the observer during the scanning process. We presented an approach based on motion tracking quantitatively to analyze the dynamic parameters of PFM on the ano-rectal angle (ARA). Perineal ultrasonography was performed on 22 asymptomatic females and nine stress urinary incontinent (SUI) patients with a broad age distribution and parity. The ventral-dorsal and cephalad-caudad movements of the ARA were resolved and kinematic parameters, in terms of displacement, trajectory, velocity and acceleration, were analyzed. The results revealed the possible mechanisms of PFM responses to prevent the urine from incontinence in fast and stress events such as coughs. The statistical analyses showed that the PFM responses of the healthy subjects and the SUI patients are significantly different in both the supine and standing experiments. (+info)
Influence of endometriosis on visceromotor and cardiovascular responses induced by vaginal distention in the rat.
(7/20)
This study examined pseudoaffective responses elicited by vaginal distention in urethane-anesthetized rats, and tested hypotheses that responses would be increased by endometriosis (ENDO) and vary with the estrous cycle. Three groups were studied: ENDO, shamENDO, and Naive. ENDO was induced by autotransplanting small pieces of uterine horn (or, for shamENDO, fat) on mesenteric arteries. Ten weeks later, rats in proestrus or metestrus were anesthetized with urethane. Distendable latex balloons were inserted into the vaginal canal. While an increasing series of vaginal distentions was delivered, changes in electromyographic activity of the external oblique musculature (visceromotor response, VMR) and mean arterial pressure (pressor) responses were simultaneously measured. Vaginal distention produced VMR and pressor responses in all groups. These responses were significantly greater in ENDO than in the other groups, and greater in proestrus than metestrus. Although the overall amount of cystic tissue was greater in proestrous than metestrous rats, there was no correlation between these amounts and VMR or pressor responses. Acute spinalization (T8-T9) and bilateral pelvic, but not hypogastric, neurectomy attenuated both VMR and pressor responses, supporting the hypothesis that vaginal nociception involves suprathoracic spinal processing of information conveyed by the pelvic nerve. These effects on VMR and pressor responses to vaginal distention parallel behavioral escape responses to the same stimuli reported previously. The findings encourage continued use of VMR and pressor responses for further investigation of mechanisms underlying pain associated with ENDO and its potential treatment. (+info)
The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis.
(8/20)
The transient receptor potential vanilloid 1 receptor (TRPV1) is an important nociceptor involved in neurogenic inflammation. We aimed to examine the role of TRPV1 in experimental colitis and in the development of visceral hypersensitivity to mechanical and chemical stimulation. Male Sprague-Dawley rats received a single dose of trinitrobenzenesulfonic acid (TNBS) in the distal colon. In the preemptive group, rats received the TRPV1 receptor antagonist JYL1421 (10 mumol/kg, i.v.) or vehicle 15 min prior to TNBS followed by daily doses for 7 days. In the post-inflammation group, rats received JYL1421 daily for 7 days starting on day 7 following TNBS. The visceromotor response (VMR) to colorectal distension (CRD), intraluminal capsaicin, capsaicin vehicle (pH 6.7) or acidic saline (pH 5.0) was assessed in all groups and compared with controls and naive rats. Colon inflammation was evaluated with H&E staining and myeloperoxidase (MPO) activity. TRPV1 immunoreactivity was assessed in the thoraco-lumbar (TL) and lumbo-sacral (LS) dorsal root ganglia (DRG) neurons. In the preemptive vehicle group, TNBS resulted in a significant increase in the VMR to CRD, intraluminal capsaicin and acidic saline compared the JYL1421-treated group (P<0.05). Absence of microscopic colitis and significantly reduced MPO activity was also evident compared with vehicle-treated rats (P<0.05). TRPV1 immunoreactivity in the TL (69.1+/-4.6%) and LS (66.4+/-4.2%) DRG in vehicle-treated rats was increased following TNBS but significantly lower in the preemptive JYL1421-treated group (28.6+/-3.9 and 32.3+/-2.3 respectively, P<0.05). JYL1421 in the post-inflammation group improved microscopic colitis and significantly decreased the VMR to CRD compared with vehicle (P<0.05, >/=30 mm Hg) but had no effect on the VMR to chemical stimulation. TRPV1 immunoreactivity in the TL and LS DRG was no different from vehicle or naive controls. These results suggest an important role for TRPV1 channel in the development of inflammation and subsequent mechanical and chemical visceral hyperalgesia. (+info)