The role of NK1 and NK3 receptors in synaptic transmission between myenteric neurons during motility reflexes in the guinea‐pig ileum was investigated by recording intracellularly the reflex responses of the circular muscle to distension or compression of the mucosal villi. Experiments were performed in a three‐chambered organ bath that enabled drugs to be selectively applied to different sites along the reflex pathways. When applied in the recording chamber, an NK1 receptor antagonist, SR140333 (100 nm), reduced by 40–50% the amplitudes of inhibitory junction potentials (i.j.ps) evoked in the circular muscle by activation of descending reflex pathways. This effect was abolished when synaptic transmission in the stimulus region was blocked with physiological saline containing 0.1 mm Ca2+ plus 10 mm Mg2+, leaving only the component of the descending reflex pathway conducted via long anally directed collaterals of intrinsic sensory neurons. SR140333 (100 nm) had no effect on descending reflex i.j.ps when applied to the stimulus region. Ascending reflexes were also unaffected by SR140333 in the stimulus region or between the stimulus and recording sites. Septide (10 nm), an NK1 receptor agonist, enhanced descending reflexes by 30–60% when in the recording chamber. [Sar9,Met(O2)11]substance P had no effect at 10 nm, but potentiated distension‐evoked reflexes at 100 nm. A selective NK3 receptor antagonist, SR142801 (100 nm), when applied to the stimulus region, reduced the amplitude of descending reflex responses to compression by 40%, but had no effect on responses to distension. SR142801 (100 nm) had no effect when applied to other regions of the descending reflex pathways. SR142801 (100 nm) only inhibited ascending reflexes when applied at the recording site. However, after nicotinic transmission in the stimulus region was blocked, SR142801 (100 nm) at this site reduced responses to compression. Contractions of the circular muscle of isolated rings of ileum evoked by low concentrations of septide, but not [Sar9,Met(O2)11]substance P, were potentiated by tetrodotoxin (300 nm). Contractile responses evoked by an NK3 receptor agonist, senktide, were non‐competitively inhibited by SR142801. After excitatory neuromuscular transmission was blocked, senktide produced inhibitory responses that were also antagonised by SR142801, but to a lesser extent and in an apparently competitive manner. These results indicate that tachykinins acting via NK1 receptors partly mediate transmission to inhibitory motor neurons. NK3 receptors play a role in transmission from intrinsic sensory neurons and from ascending interneurons to excitatory motor neurons during motility reflexes. British Journal of Pharmacology (1998) 124, 1375–1384; doi:
1 The roles of acetylcholine (ACh) and tachykinins in neuro-neuronal transmission during ascending excitatory and descending inhibitory reflexes were studied by recording intracellular reflex responses of the circular muscle to physiological stimuli. Experiments were carried out in opened segments of guineapig ileum in an organ bath that was partitioned so that three regions could be independently exposed to drugs. 2 Ascending excitatory reflexes evoked by either distension from the serosal side or compression of the mucosa were depressed by 55% and 85%, respectively, in the presence of hexamethonium (200 gM) and by 30% and 45%, respectively, by a desensitizing concentration of the selective NK3 receptor agonist, senktide (1 gM), in the chamber in which reflexes were initiated. Together, hexamethonium and senktide abolished reponses to compression. A residual response to distension persisted. This was abolished by hyoscine (1 uM).3 Hexamethonium (200 gM) abolished ascending reflexes when applied to the region between the stimulus and the recording sites, or to the recording chamber. 4 Descending reflex responses were reduced by 35% by synaptic blockade in the stimulus chamber with physiological saline containing 0.1 mM Ca2" plus 10 mM Mg2'. Senktide (1 gM) in the stimulus chamber reduced distension reflexes to the same extent as synaptic blockade, whereas hexamethonium (200 gM) and hyoscine (1 gM) depressed responses by less than 20%. Responses to compression were reduced by 40% by senktide alone, while senktide and hexamethonium together reduced responses by 60%, an effect similar to synaptic blockade. Under these conditions, hyoscine in the stimulus chamber restored reflexes evoked by distension, but did not alter those evoked by mucosal compression. 5 Total synaptic blockade in the intermediate chamber, between stimulus and recording sites, reduced descending reflex responses by more than 90%. In contrast, hexamethonium (200 gM) had no effect and hyoscine (1 gM) reduced only the responses to distension (by 30%). Senktide (1 gM) depressed responses to both stimuli by approximately 80%.6 Application of hexamethonium (200 gM) to the recording chamber depressed descending reflex responses to distension applied in the near stimulation chamber by 15%, but had no effect on responses to compression in the near chamber or to either stimulus applied in the far chamber. 7 Descending reflexes evoked by near chamber stimuli were unaffected by hyoscine (1 gM) or senktide (1 gM) applied to the recording chamber; hyoscine enhanced reflexes evoked by compression in the far chamber by 50%. 8 For the ascending excitatory reflex pathway, it is concluded that transmission from sensory neurones is mediated by ACh acting via both nicotinic and muscarinic receptors, and by tachykinins acting at NK3 receptors. Transmission from ascending interneurones appears to be predominantly via nicotinic receptors. The descending inhibitory pathways are more complex, and while transmission from sensory neurones involves nicotinic, muscarinic ...
this has resulted in substantially greater moisture use efficiency in recent years likely due to better, more timely crop management and the improved cereal varieties now used. When y was related to AvSpSM and GSP ( I May to 31 July) analyzed as separate variables, the relationship was only improved in terms of coefficient of determination (R2) value when a quadratic model was used. However, the latter did not predict the 1985 and 1986 yields as well as the y vs. MU relationship did. For fallow-seeded wheat, the relative effect of GSP on yield variability was about 5.4 times as great as that of AvSpSM; for stubble-seeded wheat it was only 1.5 times as great. GSP was equally important in affecting yields of wheat grown on fallow or stubble. The grain-filling period was confirmed as the most important for the occurrence of precipitation for both fallow-and stubble-seeded wheat, but precipitation at or near seeding time was almost as important for stubble-seeded wheat since this ensures the establishment of an adequate plant stand.
Consider the motion of a Brownian particle that initially takes place in a twodimensional plane and then after some random/unobservable time continues in the three-dimensional space. Given that only the distance of the particle to the origin is being observed, the problem is to detect the time at which the particle departs from the plane as accurately as possible. We solve this problem in the most uncertain scenario when the random/unobservable time is (i) exponentially distributed and (ii) independent from the initial motion of the particle in the plane. The solution is expressed in terms of a stopping time that minimises the probability of a false early detection and the expected delay of a missed late detection.
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