Impact of polypropylene prolapse mesh on vaginal smooth muscle in rhesus macaque.

BACKGROUND: The use of polypropylene prolapse mesh to treat pelvic organ prolapse has been limited by mesh-related complications. Gynemesh PS mesh, implanted via sacrocolpopexy in rhesus macaques, had a negative impact on the vagina with thinning of vaginal muscularis and decreased vaginal smooth muscle contractility. The negative effect was attenuated when a bioscaffold derived from urinary bladder extracellular matrix was used as a composite with Gynemesh PS. OBJECTIVE: The objective of the study was to further elucidate the impact of Gynemesh PS polypropylene mesh and MatriStem extracellular matrix bioscaffolds on the vaginal smooth muscle in terms of micromorphology of vaginal smooth muscle (muscle bundles and individual myocytes), innervation, and nerve-mediated contractile function following their implantations in a rhesus macaque model via sacrocolpopexy. STUDY DESIGN: Thirty-two middle-aged rhesus macaques were randomized to undergo either a sham surgery (sham, n = 8), or the implantation of Gynemesh PS alone (n = 8) vs composite mesh comprised of Gynemesh PS plus 2-ply MatriStem (n = 8) vs 6-ply MatriStem alone (n = 8) via sacrocolpopexy. The graft-vagina complexes were harvested 3 months later. Histomorphometrics of smooth muscle bundles and myocytes were performed by immunofluorescent labeling of alpha smooth muscle actin, caveolin-3 (membrane protein), and cell nuclei followed by confocal imaging. The cross-sectional diameters of smooth muscle bundles and individual myocytes were quantified using images randomly taken in at least 5 areas of each section of sample. Contractile proteins alpha smooth muscle actin and smoothelin were quantified by Western immunoblotting. Nerve density was measured by immunohistochemical labeling of a pan-neuron marker, PGP9.5. Nerve-mediated smooth muscle contractility was quantified using electrical field stimulation. One-way analysis of variance and appropriate post hoc tests were used for statistical comparisons. RESULTS: Compared with sham, the implantation of Gynemesh PS alone resulted in a disorganized smooth muscle morphology with the number of small muscle bundles (cross-sectional diameter less than 20 µm) increased 67% (P = .004) and the myocyte diameter decreased 22% (P < .001). Levels of contractile proteins were all decreased vs sham with alpha smooth muscle actin decreased by 68% (P = .009), low-molecular-weight smoothelin by 51% (P = .014), and high-molecular-weight smoothelin by 40% (P = .015). Nerve density was decreased by 48% (P = .03 vs sham) paralleled by a 63% decrease of nerve-mediated contractility (P = .02). Following the implantation of composite mesh, the results of measurements were similar to sham (all P > .05), with a 39% increase in the myocyte diameter (P < .001) and a 2-fold increase in the level of alpha smooth muscle actin relative to Gynemesh (P = .045). Following the implantation of MatriStem alone, the number of small muscle bundles were increased 54% vs sham (P = .002), while the other parameters were not significantly different from sham (all P > .05). CONCLUSION: The implantation of Gynemesh PS had a negative impact on the structural and functional integrity of vaginal smooth muscle evidenced by atrophic macro- and microscopic muscle morphology, decreased innervation, and impaired contractile property, consistent with a maladaptive remodeling response. The extracellular matrix bioscaffold (MatriStem), when used with Gynemesh PS as a composite (2 ply), attenuated the negative impact of Gynemesh PS; when used alone (6 ply), it induced adaptive remodeling as evidenced by an increased fraction of small smooth muscle bundles with normal contractility.

The impact of prolapse mesh on vaginal smooth muscle structure and function.

OBJECTIVE: To evaluate the impact of prolapse meshes on vaginal smooth muscle structure (VaSM) and function, and to evaluate these outcomes in the context of the mechanical and textile properties of the mesh. DESIGN: Three months following the implantation of three polypropylene prolapse meshes with distinct textile and mechanical properties, mesh tissue explants were evaluated for smooth muscle contraction, innervation, receptor function, and innervation density. SETTING: Magee-Womens Research Institute at the University of Pittsburgh. POPULATION: Thirty-four parous rhesus macaques of similar age, parity, and pelvic organ prolapse quantification (POP-Q) scores. METHODS: Macaques were implanted with mesh via sacrocolpopexy. The impact of Gynemesh(™)  PS (Ethicon; n = 7), Restorelle(®) (Coloplast; n = 7), UltraPro(™) parallel and UltraPro(™) perpendicular (Ethicon; n = 6 and 7, respectively) were compared with sham-operated controls (n = 7). Outcomes were analysed by Kruskal-Wallis ANOVA, Mann-Whitney U-tests and multiple regression analysis (P < 0.05). MEAN OUTCOME MEASURES: Vaginal tissue explants were evaluated for the maximum contractile force generated following muscle, nerve, and receptor stimulation, and for peripheral nerve density. RESULTS: Muscle myofibre, nerve, and receptor-mediated contractions were negatively affected by mesh only in the grafted region (P < 0.001, P = 0.002, and P = 0.008, respectively), whereas cholinergic and adrenergic nerve densities were affected in the grafted (P = 0.090 and P = 0.008, respectively) and non-grafted (P = 0.009 and P = 0.005, respectively) regions. The impact varied by mesh property, as mesh stiffness was a significant predictor of the negative affect on muscle function and nerve density (P < 0.001 and P = 0.013, respectively), whereas mesh and weight was a predictor of receptor function (P < 0.001). CONCLUSIONS: Mesh has an overall negative impact on VaSM, and the effects are a function of mesh properties, most notably, mesh stiffness. TWEETABLE ABSTRACT: Prolapse mesh affects vaginal smooth muscle.

Endoscopic treatment of vesicoureteral reflux with non-simultaneous involuntary detrusor contraction in chronic spinal cord injury patients with neurogenic detrusor overactivity.

OBJECTIVE: To analyze whether it is correct to use endoscopic treatment via bulking agents of vesicoureteral reflux (VUR) seen on video urodynamics with non-simultaneous involuntary detrusor contraction in chronic spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO). METHODS: A retrospective study was performed with a cohort of 76 patients (age 48.9 ± 14.4 years) (mean ± standard deviation) of both sexes with chronic SCI who underwent endoscopic treatment of VUR during the years 2008 to 2011. Patients were subjected to clinical examinations and video urodynamic studies preoperatively and 22 ± 11.4 months after the intervention. RESULTS: Resolution of VUR was achieved in 46 cases (61%). Cured patients had a statistically significant younger age and showed stress urinary incontinence more frequently. On the contrary, a greater grade of VUR, presence of bilateral reflux and presence of NDO were positively associated with treatment failure. The variables that independently influenced the cure of the reflux were NDO and reflux grade. CONCLUSIONS: The failure rate was high in patients with NDO, even though the reflux was not synchronous with involuntary detrusor contraction, and therefore these patients should have NDO eradicated before doing any anti-reflux procedures.

Organization of Buccal Cone Musculature in the Pteropod Mollusc Clione limacina.

The pteropod mollusc Clione limacina is a feeding specialist, preying on shelled pteropods of the genus Limacina. Specialized prey-capture structures, called buccal cones, are hydraulically everted from within the mouth to capture the prey. Once captured, the prey is manipulated so the shell opening is over the mouth of Clione. Analyses of high-speed cine sequences of prey capture suggest that the mouth is actively opened rather than passively forced open by buccal cone eversion. The inflated buccal cones are initially straight and form a wide angle (maximum, 113°) prior to prey contact. Individual buccal cones bend orally following prey contact, suggesting a sensory trigger. To determine the muscular basis of buccal cone movements, the musculature of the buccal cones is described. Three distinct muscle fiber types include circular smooth muscle, longitudinal smooth muscle, and longitudinal striated muscle. The organization, distribution, and innervation of the muscle types suggest that circular muscle is used during buccal cone eversion, longitudinal smooth muscle is used for buccal cone withdrawal, and longitudinal striated muscle is used for oral bending of the buccal cones after prey contact and for manipulation of the prey.

Effects of mandibular advancement on upper airway dynamics in awake normal subjects: a pilot study with phrenic nerve stimulation.

BACKGROUND: Mandibular advancement (MA) can be an alternative to continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea syndrome. This study was designed to describe its effects on upper airway mechanics. METHODS: Six awake healthy subjects (four men, 31+/-8 years, body mass index (BMI) 25+/-2kg/m2) were studied supine. Phrenic stimulation was used to measure pressure-flow relationships in response to diaphragm contractions without pre-activation of upper airway dilators during progressive MA. RESULTS: Phrenic stimulation consistently induced flow limitation (initial peak V'-t1, corresponding to the limiting pressure; reduction to a nadir V'-t2; reincrease to a second peak V'-t3). The upper airway resistances were negatively correlated with MA. Their values at 4mm were significantly lower than at baseline. Further MA reduced resistances. CONCLUSIONS: As with CPAP, MA in normal subjects decreases the propensity of the upper airway to collapse in response to a negative pressure pulse.

Dendritic architecture of nucleus ambiguus motoneurons projecting to the upper alimentary tract in the rat.

The motor innervation for palatal, pharyngeal, laryngeal, and esophageal muscles originates within the nucleus ambiguus. Although the viscerotopic organization of the upper alimentary tract in the nucleus ambiguus has been extensively studied, little information concerning the dendritic arborization of nucleus ambiguus motoneurons is available. The neural tracer cholera toxin-horseradish peroxidase, which is particularly effective at revealing dendrites of retrogradely labeled neurons, was used to determine the dendritic architecture and organization of nucleus ambiguus motoneurons. In 72 rats, cholera toxin-horseradish peroxidase in volumes of 1.0-18 microliters was directly applied under pressure to the musculature of various sites along the upper alimentary tract. Motoneurons innervating the soft palate, pharynx, cricothyroid muscle, and cervical esophagus were all found to have extensive dendrites that extended into the adjacent reticular formation with a distinct pattern for each muscle group. In contrast, the dendrites of motoneurons innervating the thoracic and subdiaphragmatic esophagus were confined to the compact formation of the nucleus ambiguus. Dendritic bundling within the confines of the nucleus ambiguus was prominent following injection of tracer into the soft palate, pharynx, and esophagus. The bundles were primarily oriented in a rostrocaudal direction. These data suggest that the extensive extranuclear dendritic arborization of motoneurons innervating the soft palate, pharynx, larynx, and cervical esophagus provide a wide ranging target for multiple central afferents that may be involved in the differential control of muscles that participate in multiple complex motor functions. The lack of extensive extranuclear dendrites of motoneurons innervating the distal esophagus suggest that they receive focused central afferents. The prominent bundling of dendrites within the nucleus ambiguus may provide for synchronization of motoneurons innervating a specific muscle and perhaps for synchronization of motoneurons innervating different muscles acting in sequence.

Rat sciatic nerve regeneration through a micromachined silicon chip.

The capacity of regenerating nerve fibres to grow through a perforated silicon chip was tested using the silicone chamber model for nerve regeneration. The chips were fabricated as circular membranes, 4 mm in diameter, thickness 60 microns, with a perforated area, 2 mm in diameter, in the centre. Three types of chips were fabricated utilizing anisotropic etching. The chips were glued with silicone adhesive between two halves of silicone rubber tubing (total length 8 mm, inner diameter 1.8 mm, outer diameter 3.0 mm) which was used to bridge a 4 mm gap between the proximal and distal nerve stumps of a transected rat sciatic nerve. The capacity of regenerating nerve fibres to grow through the holes of the chip was analysed by light and scanning electron microscopy after 4 or 16 weeks of regeneration. Furthermore, the muscle contractility force of the gastrocnemius muscle was measured after 16 weeks of regeneration and compared as a percentage of the contralateral uninjured side. Nerves generated through chips with hole diameters of 10 or 50 microns were morphological and functional failures. The nerve structures distal to chips with hole diameters of 100 microns contained many myelinated nerve fibres in a minifascicular pattern after both 4 and 16 weeks of regeneration. The muscle contractility force was 56% of that of contralateral control muscles.

Influence of polyethylene-glycol-superoxide dismutase and combined depletion and repletion of antioxidants on nitrergic relaxation in the pig gastric fundus.

In circular smooth muscle strips of porcine gastric fundus, polyethylene-glycol-superoxide dismutase, a membrane-permeable analogue of endogenous copper/zinc (Cu/Zn) superoxide dismutase, reversed the inhibitory effect of the superoxide anion generator 6-anilino-5,8-quinolinedione (LY83583) on electrically induced nitrergic relaxations of fundic tissues which are depleted of the endogenous antioxidant Cu/Zn superoxide dismutase by diethyldithiocarbamate, to the same extent as exogenously added Cu/Zn superoxide dismutase. Addition of a second antioxidant together with Cu/Zn superoxide dismutase does not result in a higher degree of reversal of the inhibitory effect of LY83583. Depletion of either tissue glutathione or tissue catalase in combination with diethyldithiocarbamate does not increase the inhibitory action of LY83583 or the nitric oxide (NO)-scavenger hydroxocobalamin upon nitrergic relaxations (electrically induced or by exogenous NO) when compared to their action in the presence of diethyldithiocarbamate alone. In conclusion, these results demonstrate that endogenous Cu/Zn superoxide dismutase is the essential antioxidant responsible for safeguarding peripheral nitrergic neurotransmission, whereby extracellular protection of endogenous NO is most important.

Muscarinic receptor subtypes modulating smooth muscle contractility in the urinary bladder.

Normal physiological voiding as well as generation of abnormal bladder contractions in diseased states is critically dependent on acetylcholine-induced stimulation of contractile muscarinic receptors on the smooth muscle (detrusor) of the urinary bladder. Muscarinic receptor antagonists are efficacious in treating the symptoms of bladder hyperactivity, such as urge incontinence, although the usefulness of available drugs is limited by undesirable side-effects. Detrusor smooth muscle is endowed principally with M2 and M3 muscarinic receptors with the former predominating in number. M3 muscarinic receptors, coupled to stimulation of phosphoinositide turnover, mediate the direct contractile effects of acetylcholine in the detrusor. Emerging evidence suggests that M2 muscarinic receptors, via inhibition of adenylyl cyclase, cause smooth muscle contraction indirectly by inhibiting sympathetically (beta-adrenoceptor)-mediated relaxation. In certain diseased states, M2 receptors may also contribute to direct smooth muscle contraction. Other contractile mechanisms involving M2 muscarinic receptors, such as activation of a non-specific cationic channel and inactivation of potassium channels, may also be operative in the bladder and requires further investigation. From a therapeutic standpoint, combined blockade of M2 and M3 muscarinic receptors would seem to be ideal since this approach would evoke complete inhibition of cholinergically-evoked smooth muscle contractions. However, if either the M2 or M3 receptor assumes a greater pathophysiological role in disease states, then selective antagonism of only one of the two receptors may be the more rational approach. The ultimate therapeutic strategy is also influenced by the extent to which pre-junctional M1 facilitatory and M2 inhibitory muscarinic receptors regulate acetylcholine release and also which subtypes mediate the undesirable effects of muscarinic receptor blockade such as dry mouth. Finally, the consequence of muscarinic receptor blockade in the central nervous system on the micturition reflex, an issue which is poorly studied and seldom taken into consideration, should not be ignored.

The relationship between feed intake and frequency of the migrating motor complex in domestic turkeys: is there a cephalic phase?

Two studies were performed in order to test for the presence of a cephalic inhibition of migrating motor complexes (MMC) in domestic turkeys. Birds were implanted with two or three strain gauge transducers on the ileum and subjected to one of two different protocols. In Study 1 recordings of ileal motility were made under three feeding conditions: fed, fasted, and with feed pans in place before the birds but covered with plexiglass. In Study 2 the birds were either fasted, fasted with feed pans returned as soon as an MMC registered in the most orad gauge, or fasted with a minor disruption in the room (to simulate feed pan return) as soon as an MMC registered in the most orad gauge. Data from trials involving plexiglass plates did not differ significantly from data from fasted birds, and both differed significantly from the data from fed birds. Likewise, no significant differences were seen among any of the three feeding categories of Study 2. The present data show that neither the anticipation of eating, nor the presence of feed in the mouth and esophagus seem to directly influence the initiation or propagation of ileal MMC contractile activity in turkeys, supporting the view that extrinsic neural pathways are not responsible for the inhibition of the MMC.

Corrosion products from dental alloys and effects of mercuric and cupric ions on a neuroeffector system.

The release of corrosion products during long-term immersion in vitro of dental alloys, with particular reference to dissimilar alloys in contact has been studied. The effects of Hg2+ and Cu2+ in low concentrations on the guinea-pig ileum have also been studied. The following conclusions were drawn: In an aggressive solution the release of elements from amalgams could be continuous and subsurface corrosion could cause a considerable increase in the corrosion products released. The change in microstructure observed in cross-sections of the corroded specimens was related to the amounts of corrosion products released into the saline solution. In an aggressive solution the corrosion products could increase when amalgams, Co-Cr, and Ni-Cr alloys are in contact with gold alloys, a high-Cu amalgam is in contact with a conventional amalgam, a type III gold alloy is in contact with gold alloys for metallo-ceramic purposes. The high-Cu amalgams released more corrosion products into the saline solution than a conventional one. Greater quantities of corrosion products were released from amalgams at pH 4 than at pH 6. Hg2+ and Cu2+ both had diverse and dose-dependent effects on the guinea-pig ileum. In low concentrations, 10nM, both ions exerted effects, probably on the muscle cell membrane.

Neuromuscular control of the oropharynx and esophagus in health and disease.

The oropharynx and esophagus convey swallowed materials from the mouth to the stomach and protect the airways from aspiration. These functions are subserved by complex neuromuscular interactions that coordinate the timing of the peristaltic contractions of the swallowing organs. The oropharynx and upper esophagus are composed of striated muscle, whereas the distal esophagus is composed of smooth muscle. The central nervous system completely controls peristalsis in the striated muscle organs. In the distal esophagus, neuromuscular mechanisms intrinsic to the esophagus control peristalsis. Diseases of the striated muscle, of the smooth muscle, or of the nervous system can lead to a derangement of peristalsis and disrupt the propulsion of swallowed materials to the stomach.

Polyphosphoinositides, generation of second messengers, myosin light chain phosphorylation and contraction in rabbit iris sphincter smooth muscle.

There is general agreement now that elevation of intracellular calcium ion concentration [( Ca2+]i) mediates the physiological actions of a number of hormones, neurotransmitters and other pharmacological agents. In smooth muscle one way by which these agents elevate [Ca2+]i and induce contraction involves formation of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). Our initial observation that the muscarinic-stimulated breakdown of PIP2 into IP3 and DG in the iris smooth muscle is a primary event that could couple activated receptors to contraction is now supported by the following: 1. In the iris sphincter contractions by carbachol (CCh) indicated close correlations, using different concentrations of CCh, atropine- and pirenzepine antagonists, time course, temperature and Ca2+, between the stimulated hydrolysis of PIP2, myosin light chain (MLC) phosphorylation and muscle contraction. Further, studies on the relationships between receptor occupancy of muscarinic acetylcholine receptors in this tissue, measured by [3H]QNB binding, and the CCh-stimulated PIP2 hydrolysis, MLC phosphorylation and contraction revealed that all of these responses are coupled to the M2 receptor subtype. 2. NaF, which activates G proteins by promoting the dissociation of their subunits, produced a concentration-dependent activation of phospholipase C, measured as IP3 accumulation, and contraction in the iris sphincter muscle. 3. In permeabilized smooth muscle fibers, IP3 has been shown to release Ca2+ from the SR and induce contraction. 4. In the iris sphincter, as well as in other smooth muscles, phorbol 12,13-dibutyrate, which mimics the action of DG, induced MLC phosphorylation and contraction in a dose- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple axonal spike initiation zones in a motor neuron: serotonin activation.

The lateral gastric (LG) motor neuron of the stomatogastric nervous system of the crab Cancer borealis has a large soma in the stomatogastric ganglion (STG). The LG motor neuron makes inhibitory synaptic connections within the neuropil of the STG, and also projects to the periphery, where it innervates a series of muscles that control the movements of the lateral teeth of the gastric mill. The LG motor neuron has a spike initiation zone close to its neuropilar integrative regions, from which spikes propagate orthodromically to the muscles. Additionally, under certain conditions, the LG neuron can initiate spikes at peripheral axonal sites that can be 0.5-2.0 cm from the STG. Peripherally initiated spikes propagate antidromically into the STG and also propagate to the muscle. The peripheral spike initiation zones are often active in combined preparations in which the muscles are left attached. When the muscles are removed, depolarization of the LG soma together with 5-HT applied to the motor nerve also evokes peripheral spike initiation. At a given 5-HT concentration, the duration of the trains of antidromic spikes can be controlled by current injection into the soma, suggesting the presence of a slow voltage-dependent conductance in the LG axon. The antidromic spikes contribute to lengthening of the duration of contraction in some of the muscles innervated by the LG, but do not evoke IPSPs onto LG follower neurons. Thus, the LG neuron can send different signals to its peripheral and central targets.

Anatomic relationships of the orbital muscle of Müller in human fetuses.

A study was carried out in twenty human fetuses on the relationships of the orbital muscle of Müller. This muscle forms a lamina of smooth muscle fibres that cover the inferior orbital fissure. The latter is very wide during the fetal period because ossification of the bones that delimit this region is still incomplete. Some fibres of the orbital muscle extend along the superior orbital fissure under the inferior ophthalmic vein and the lower wall or floor of the cavernous sinus. This association suggests a possible influence on autonomically mediated vascular dynamics.

The effect of alpha-adrenergic stimulation in stress incontinence.

The urethra is innervated by adrenergic fibres and its smooth muscle is equipped mainly with alpha-adrenoreceptors. Norephedrine chloride, which is an alpha-stimulating agent, has been proposed as therapy for stress incontinence, since it was shown to increase the maximum urethral pressure at rest. For further study of the effect of norephedrine chloride on the urethal closure pressure at rest and in a dynamic situation, we examined ten severely stress-incontinent women before and after three weeks of treatment with this agent (100 mg by mouth twice daily). The urethral closure pressure at rest, between coughs of varied strength and at the precise moment of stress were recorded. The margin to leakage, the tone of the urethral wall and the transmission of pressure from abdomen to urethra were also among the estimated factors. No improvement was found in any of these respects. Alpha stimulation in this form therefore seems ineffective in severe stress incontinence and is not an alternative to surgical treatment.

Intravesical therapy options for neurogenic detrusor overactivity.

STUDY DESIGN: Review article. SETTING: Neuro-Urology, Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland. OBJECTIVES: This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends. METHODS: The available literature was reviewed using medline services. RESULTS: Oral anticholinergic drugs are widely used to treat detrusor overactivity, but they are ineffective in some patients or cause systemic side effects such as blurred vision or dry mouth. As an alternative, topical therapy strategies have been suggested to achieve a profound inhibition of the overactive detrusor and to avoid high systemic drug levels. Currently available intravesical treatment options either act on the afferent arc of the reflex such as local anaesthetics or vanilloids or on the efferent cholinergic transmission to the detrusor muscle such as intravesical oxybutynin or botulinum toxin. Although an established and effective therapy, intravesical oxybutynin is not widely used. Evidence for clinical significance of intravesical atropine and local anaesthetic is missing. Intravesical capsaicin has been shown to improve clinical and urodynamic parameters, but cause pain in some patients. The intravesical instillation of resiniferatoxin and the injection of botulinum-A toxin into the detrusor muscle are promising new options; however, randomised placebo-controlled studies to prove their safety and efficacy are still missing. CONCLUSION: Intravesical treatment strategies in patients with neurogenic detrusor overactivity may provide alternatives to established therapies such as oral anticholinergics. The selectivity of the intravesical treatment and the reduction or even the absence of side effects are major advantages of this topical approach.

On the function of myoepithelial cells in salivary glands.

1. In dogs under chloralose-urethane anaesthesia the submaxillary duct was cannulated and connected either to an open outflow system, in which saliva displaced water, or to a closed pressure recording system.2. The secretory cells, which are supplied with beta-adrenoreceptors, were stimulated with isoprenaline, adrenaline or sympathetic nerve stimulation. Myoepithelial cells, supplied with alpha-receptors, were activated with phenylephrine, adrenaline or sympathetic stimulation, and also with bradykinin. To abolish alpha-receptor stimulating effects of adrenaline and sympathetic nerve stimulation, dihydroergotamine, phenoxybenzamine and phentolamine were used.3. When the secretory cells were activated alone, saliva flowed from the salivary duct, but the flow started late and only a moderately high pressure could be produced in the closed system. Saliva appeared much earlier in the duct when secretion was combined with myoepithelial contraction, and a much higher pressure could be built up in the duct system.4. It is concluded that rapid emptying of saliva in the mouth and a maintained flow at a high rate of the viscous saliva is promoted by contractions of the myoepithelial cells.

A neurokinin-1 receptor antagonist reduced hypersalivation and gastric contractility related to emesis in dogs.

The roles of tachykinin neurokinin-1 (NK1) receptors in the induction of fictive retching, hypersalivation, and gastric responses associated with emesis induced by abdominal vagal stimulation were studied in paralyzed, decerebrated dogs. Vagal stimulation induced gradual increases in salivary secretion and activity of the parasympathetic postganglionic fibers to the submandibular gland, relaxation of the gastric corpus and antrum, and fictive retching. However, hypersalivation and increased nerve activity were suppressed and antral contractility was enhanced during fictive retching. An NK1 receptor antagonist, GR-205171, abolished the enhancement of antral contractility and fictive retching but had no effect on corpus and antral relaxation. Hypersalivation and increased nerve activity were inhibited by GR-205171 but were not completely abolished. Reflex salivation by lingual nerve stimulation was unaffected. These results suggest that GR-205171 acts on the afferent pathway in the bulb and diminishes hypersalivation and antral contraction related to emesis as well as fictive retching but does not affect gastric relaxation or hypersalivation induced by the vagovagal, vagosalivary, and linguosalivary reflexes.