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Polyamines in intestinal and pancreatic adaptation.

The intestinal mucosa is a rapidly proliferative tissue, with a highly dynamic cell population. Its total cellular mass is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors, and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal adaptation. Similarly, the same factors appear essential for the maintenance of exocrine pancreatic structure and function. The polyamines (putrescine, spermidine, and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase, ODC) are important for many cell growth processes, and may play important roles in intestinal and pancreatic adaptation. During intestinal adaptation in response to jejunectomy, lactation and pancreatico-biliary diversion (PBD), intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increases in ODC and polyamines are suppressed, and intestinal adaptation is abrogated. In pancreatic hyperplasia induced by caerulein, pancreatic polyamines are increased. With DFMO administration, caerulein-induced increases in pancreatic DNA synthesis were inhibited and pancreatic hypertrophy was partially suppressed. PBD-induced pancreatic hypertrophy, however, was not affected by DFMO. Thus, the role of polyamines in the adaptation of the pancreas, with a relatively quiescent proliferative status, is as yet undefined. It seems clear, however, that the induction of ODC and the resultant increase in polyamine biosynthesis are critical for the normal growth and especially for adaptive hyperplasia of the intestinal mucosa.

Adaptation, Physiological↗

Adaptation in hair cells.

Hair cells adapt to sustained deflections of the hair bundle via Ca(2+)-dependent negative feedback on the open probability of the mechanosensitive transduction channels. A model posits that adaptation relieves the input to the transduction channels--force applied by elastic tip links between stereocilia--by repositioning the insertions of the links in the stereocilium. The tip link insertion and transduction channel are dragged by myosins moving on the stereocilium's actin core. This model accounts for many aspects of adaptation in hair cells of the frog saccule, where adaptation time constants are tens of milliseconds. Adaptation in hair cells of the turtle cochlea is much faster, possibly reflecting a more direct mechanism such as Ca2+ binding to the transduction channel. Adaptation mechanisms attenuate the transduction current at low frequencies and may be tuned to different corner frequencies according to the stimulus demands of the inner ear organ. Other sites of adaptation in the inner ear include accessory structures, voltage-dependent properties of hair cells, and afferent transmitter release. A remaining challenge is to understand how these processes work together to shape the output of the inner ear to natural stimuli.

Acoustic Stimulation↗

Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats.

Exposure to higher levels of fat in the diet increases the secretion of fat-digesting enzymes in pancreatic juice. This study examines the functional consequences of this phenomenon and demonstrates that adapting rats to high fat (triglyceride) loads increases the release of cholecystokinin (CCK) and the pancreatic secretory response to intraduodenal fat. Lipolytic activity in the small intestine was also higher in adapted rats. Exchanging pancreatic juice from unadapted rats with pancreatic juice from adapted rats decreased the response to fat in adapted rats and increased the response to fat in unadapted rats. Infusing oleic acid into unadapted rats stimulated CCK secretion and pancreatic exocrine secretion to levels observed with triglycerides in adapted rats. Pancreatic exocrine secretion in response to intraduodenal fat in rats adapted to a high-fat (20%) diet were significantly higher than the responses seen in rats fed a low-fat (5%) diet. Adaptation to fat increases the pancreatic secretory and plasma CCK responses to fat, apparently by increasing the efficiency of triglyceride digestion and thereby increasing CCK release.

Adaptation, Physiological↗

Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats.

Exercise training produces a vast array of physiological adaptations, ranging from changes in metabolism to muscle mitochondrial biogenesis. Researchers studying the physiological effects of exercise often use animal models that employ forced exercise regimens that include aversive motivation, which could activate the stress response. This study examined the effect of forced treadmill running (8 wk) on several physiological systems that are sensitive to training and stress. Forced treadmill running produced both positive and negative physiological adaptations. Indicative of positive training adaptations, exercised male Sprague-Dawley rats had a decrease in body weight gain and an increase in muscle citrate synthase activity compared with sedentary controls. In contrast, treadmill running also resulted in the potentially negative adaptations of adrenal hypertrophy, thymic involution, decreased serum corticosteroid binding globulin, elevated lymphocyte nitrite concentrations, suppressed lymphocyte proliferation, and suppressed antigen-specific IgM. Such alterations in neuroendocrine tissues and immune responses are commonly associated with chronic stress. Thus treadmill running produces both positive training adaptations and potentially negative adaptations that are indicative of chronic stress. Researchers employing forced activity need to be aware that this type of exercise procedure also produces physiological adaptations indicative of chronic stress and that these changes could potentially impact other measures of interest.

Adaptation, Physiological↗

Adaptive responses to Na(+)-coupled solute transport and osmotic cell swelling in salamander proximal tubule.

Measurements of basolateral membrane potential and relative K+ conductance were performed in isolated perfused proximal tubules from Ambystoma. To investigate adaptive increases in basolateral membrane K+ conductance (gK) associated with Na(+)-solute cotransport, measurements were made comparing transport of glucose and alanine, with changes caused by hypotonicity- and solute-induced cell swelling. Luminal perfusion with alanine produced results consistent with an adaptive increase in gK; perfusion with glucose failed to show this response. Hypotonic peritubular solutions also produced results consistent with an adaptive increase in gK, but isosmotic increases of peritubular glucose sufficient to swell the cells failed to produce this. No changes in the responses to luminal perfusion with alanine or glucose were induced by hypotonic peritubular solutions. With a high concentration of glucose in isosmotic peritubular solutions, perfusion of the lumen with glucose now produced results consistent with an adaptive increase in gK. Isosmotic peritubular solutions containing urea produced adaptive changes similar to those observed using hypotonic peritubular solutions, but when glucose was subsequently added to the lumen, no further adaptive response occurred. We conclude that cell swelling alone is insufficient to explain the mechanisms involved in the adaptive responses of gK occurring during Na(+)-solute cotransport in the salamander proximal tubule.

Adaptation, Physiological↗

Adaptation of the outer medullary collecting duct to metabolic acidosis in vitro.

Metabolic acidosis in vivo, as well as in vitro (1 h at pH 6.8 followed by 2 h at pH 7.4) stimulates H+-ATPase-dependent H+ secretion in outer medullary collecting ducts from the inner stripe (OMCDi) (S. Tsuruoka and G. J. Schwartz. J. Clin. Invest. 99: 1420-1431, 1997). Another group has shown that the adaptation to metabolic acidosis in vivo is mediated by an apical polarization of H+ pumps without an increase in total H+ pump mRNA or protein (B. Bastani, H. Purcell, P. Hemken, D. Trigg, and S. Gluck. J. Clin. Invest. 88: 126-136, 1991). To further address the mechanism of adaptation, we measured net HCO-3 absorption before and after applying protein/RNA synthesis and signal transduction inhibitors during the 1 h of low pH and a cytoskeletal inhibitor during the entire 3-h incubation. Net HCO-3 transport, measured by microcalorimetry, increased approximately 33% after in vitro acidosis. This increase was prevented by application during the first hour of anisomycin (10 microM) or actinomycin D (4 microM), but not by anisomycin applied during the 2-h incubation at pH 7.4. Similar results were obtained with the cell calcium chelator, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM, 20 microM), the calmodulin antagonist, calmidazolium (30 nM), the endoplasmic reticulum Ca-ATPase inhibitor, thapsigargin (100 nM), and the protein kinase C (PKC) inhibitor, staurosporine (100 nM), applied during the 1 h at pH 6.8, but not with BAPTA-AM or thapsigargin used during the 2-h incubation at pH 7. 4. Colchicine (10 microM) applied during the entire 3-h incubation also prevented this adaptive increase in H+ secretion, whereas lumicolchicine (10 microM, the inactive congener) did not. Colchicine also reversibly prevented any adaptive increases in transepithelial positive voltage. Thus the adaptation to acidosis in vitro required RNA and protein synthesis, changes in intracellular calcium and PKC activity, and intact microtubules. Time was required for the adaptation to occur, as the increase in HCO-3 transport was small after <3-h incubation. Protein synthesis and changes in cell calcium were critical during the initial period of low pH but not once the acid stimulus had been removed. Exocytosis of H+ pumps appears to occur continually during the entire 3-h incubation. These data would suggest that the synthesis and regulation of proteins involved in shuttling H+ pumps in cytoplasmic vesicles to the apical membrane via exocytosis are important for the OMCDi to adapt to low pH in vitro and probably to metabolic acidosis in vivo.

Acidosis↗

Adaptive changes in cats after long-term exposure to various temperatures.

Two groups of cats were exposed to 5 and 30 degrees C, respectively for 24 mo in climatic chambers under artificial illumination. Then the ambient temperatures were reversed for both groups for another 36 mo. The group adapted to cold for 36 mo showed an increase in fur growth (+35%), an increase in resting metabolism (+20%), and a shift in threshold of the cold-induced metabolic response to 8 degrees C lower ambient temperatures. Norepinephrine (0.4 mg . kg-1) elicited nonshivering thermogenesis (+37%) in the cold-adapted animals but was ineffective in the warm-adapted ones. Fur insulation at thermoneutrality was 55% higher in the cold-adapted cats. During acute exposure to -5 degrees C, tissue insulation decreased in both groups; fur insulation increased by 34% in the warm-adapted cats but remained nearly constant in the cold-adapted animals. At all ambient temperatures cold-adapted cats had higher (+0.4 degrees C) rectal temperatures. Body weight was not significantly different in both groups, although the cats living in the cold had a 45% higher metabolism. This was compensated by an increased food consumption.

Adaptation, Physiological↗

Exercise training-induced coronary vascular adaptation.

Aerobic exercise training induces an increase in coronary vascular transport capacity. This increased transport capacity is the result of increases in both blood flow capacity and capillary exchange capacity. These functional changes are the result of two major types of adaptive responses, structural vascular adaptation and altered control of vascular resistance. Structural vascular adaptation occurs in response to exercise training in at least two forms, increases in the cross-sectional area of the proximal coronary arteries and angiogenesis. Angiogenesis has been demonstrated in that training causes moderate cardiac hypertrophy while maintaining or increasing capillary density and increasing arteriolar density. Training-induced changes in coronary vascular control have been shown to include altered coronary responses to vasoactive substances, changes in endothelium-mediated vasoregulation, and alterations in the cellular-molecular control of intracellular free Ca2+ in both endothelial and vascular smooth muscle cells isolated from coronary arteries of exercise-trained animals. The signal or signals for these adaptive responses remain unknown. The hypothesis that the adaptive strategy entails maintenance of normal shear stress in coronary arterial vessels is discussed. We propose that as a result of training-induced structural vascular adaptations and alterations in the control of vascular resistance, shear stress throughout the coronary vasculature is returned to the level present in sedentary animals. The signal for adaptation may be peak shear stress during exercise and/or average shear stress over a 24-h period of time.

Adaptation, Physiological↗

Superresistance against hypoxia after preliminary adaptation to repeated stress.

The study investigated the influence of adaptation to stress on resistance to hypoxia. After rats were adaptated to moderate restraint stress, they were anesthetized and exposed to 6% O2. Adaptation increased tidal volume by 2.6-fold, lung and alveolar ventilation by 1.6- and 1.8-fold, respectively, and O2 consumption by 1.6-fold; limited lactate accumulation in the liver by 2-fold, in the heart by 34%, in the lung by 36%, and in the blood by 36%; and elevated pH. At the same time, preliminary adaptation to stress inhibited the hypoxic activation of lipolysis and peroxidation in all tissues. The concentration of lipid peroxides decreased after adaptation by 1.3- to 1.5-fold in different organs, whereas the content of free fatty acids diminished by 1.7- to 2.3-fold. Finally, after adaptation, mortality decreased under severe hypoxia by 6.5-fold. Thus, the data suggest that the cross-protective effect of adaptation was achieved by the economization of respiration and circulation, by marked augmentation in the ability of tissue to utilize blood O2, and by the limitation of processes that are able to damage tissue membranes, namely, acidosis, lipolysis, and lipid peroxidation.

Acid-Base Equilibrium↗

Training-induced adaptive plasticity in human somatosensory reflex pathways.

This paper reviews evidence supporting adaptive plasticity in muscle and cutaneous afferent reflex pathways induced by training and rehabilitative interventions. The perspective is advanced that the behavioral and functional relevance of any intervention and the reflex pathway under study should be considered when evaluating both adaptation and transfer. A cornerstone of this concept can be found in acute task-dependent reflex modulation. Because the nervous system allows the expression of a given reflex according to the motor task, an attempt to evaluate the training adaptation should also be evoked under the same conditions as training bearing in mind the functional role of the pathway under study. Within this framework, considerable evidence supports extensive adaptive plasticity in human muscle afferent pathways in the form of operant conditioning, strength training, skill training, and locomotor training or retraining. Directly comparable evidence for chronic adaptation in cutaneous reflex pathways is lacking. However, activity-dependent plasticity in cutaneous pathways is documented particularly in approaches to neurological rehabilitation. Overall, the adaptive range for human muscle afferent reflexes appears bidirectional (that is, increased or reduced amplitudes) and on the order of 25-50%. The adaptive range for cutaneous pathways is currently uncertain.

Action Potentials↗

Interlimb coordination during locomotion: what can be adapted and stored?

Interlimb coordination is critically important during bipedal locomotion and often must be adapted to account for varying environmental circumstances. Here we studied adaptation of human interlimb coordination using a split-belt treadmill, where the legs can be made to move at different speeds. Human adults, infants, and spinal cats can alter walking patterns on a split-belt treadmill by prolonging stance and shortening swing on the slower limb and vice versa on the faster limb. It is not known whether other locomotor parameters change or if there is a capacity for storage of a new motor pattern after training. We asked whether adults adapt both intra- and interlimb gait parameters during split-belt walking and show aftereffects from training. Healthy subjects were tested walking with belts tied (baseline), then belts split (adaptation), and again tied (postadaptation). Walking parameters that directly relate to the interlimb relationship changed slowly during adaptation and showed robust aftereffects during postadaptation. These changes paralleled subjective impressions of limping versus no limping. In contrast, parameters calculated from an individual leg changed rapidly to accommodate split-belts and showed no aftereffects. These results suggest some independence of neural control of intra- versus interlimb parameters during walking. They also show that the adult nervous system can adapt and store new interlimb patterns after short bouts of training. The differences in intra- versus interlimb control may be related to the varying complexity of the parameters, task demands, and/or the level of neural control necessary for their adaptation.

Adaptation, Physiological↗

Partial ablations of the flocculus and ventral paraflocculus in monkeys cause linked deficits in smooth pursuit eye movements and adaptive modification of the VOR.

The vestibuloocular reflex (VOR) generates compensatory eye movements to stabilize visual images on the retina during head movements. The amplitude of the reflex is calibrated continuously throughout life and undergoes adaptation, also called motor learning, when head movements are persistently associated with image motion. Although the floccular-complex of the cerebellum is necessary for VOR adaptation, it is not known whether this function is localized in its anterior or posterior portions, which comprise the ventral paraflocculus and flocculus, respectively. The present paper reports the effects of partial lesions of the floccular-complex in five macaque monkeys, made either surgically or with stereotaxic injection of 3-nitropropionic acid (3-NP). Before and after the lesions, smooth pursuit eye movements were tested during sinusoidal and step-ramp target motion. Cancellation of the VOR was tested by moving a target exactly with the monkey during sinusoidal head rotation. The control VOR was tested during sinusoidal head rotation in the dark and during 30 degrees/s pulses of head velocity. VOR adaptation was studied by having the monkeys wear x2 or x0.25 optics for 4-7 days. In two monkeys, bilateral lesions removed all of the flocculus except for parts of folia 1 and 2 but did not produce any deficits in smooth pursuit, VOR adaptation, or VOR cancellation. We conclude that the flocculus alone probably is not necessary for either pursuit or VOR learning. In two monkeys, unilateral lesions including a large fraction of the ventral paraflocculus produced small deficits in horizontal and vertical smooth pursuit, and mild impairments of VOR adaptation and VOR cancellation. We conclude that the ventral paraflocculus contributes to both behaviors. In one monkey, a bilateral lesion of the flocculus and ventral paraflocculus produced severe deficits smooth pursuit and VOR cancellation, and a complete loss of VOR adaptation. Considering all five cases together, there was a strong correlation between the size of the deficits in VOR learning and pursuit. We found the strongest correlation between the behavior deficits and the size of the lesion of the ventral paraflocculus, a weaker but significant correlation for the full floccular complex, and no correlation with the size of the lesion of the flocculus. We conclude that 1) lesions of the floccular complex cause linked deficits in smooth pursuit and VOR adaptation, and 2) the relevant portions of the structure are primarily in the ventral paraflocculus, although the flocculus may participate.

Adaptation, Physiological↗

Neuromotor noise limits motor performance, but not motor adaptation, in children.

Children do not typically appear to move with the same skill and dexterity as adults, although they can still improve their motor performance in specific tasks with practice. One possible explanation is that their motor performance is limited by an inherently higher level of movement variability, but that their motor adaptive ability is robust to this variability. To test this hypothesis, we examined motor adaptation of 43 children (ages 6-17) and 12 adults as they reached while holding the tip of a lightweight robot. The robot applied either a predictable, velocity-dependent field (the "mean field") or a similar field that incorporated stochastic variation (the "noise field"), thereby further enhancing the variability of the subjects' movements. We found that children exhibited greater initial trial-to-trial variability in their unperturbed movements but were still able to adapt comparably to adults in both the mean and noise fields. Furthermore, the youngest children (ages 6-8) were able to reduce their variability with practice to levels comparable to the remaining children groups although not as low as adults. These results indicate that children as young as age 6 possess adult-like neural systems for motor adaptation and internal model formation that allow them to adapt to novel dynamic environments as well as adults on average despite increased neuromotor or environmental noise. Performance after adaptation is still more variable than adults, however, indicating that movement inconsistency, not motor adaptation inability, ultimately limits motor performance by children and may thus account for their appearance of incoordination and more frequent motor accidents (e.g., spilling, tripping). The results of this study also suggest that movement variability in young children may arise from two sources--a relatively constant, intrinsic source related to fundamental physiological constraints of the developing motor system and a more rapidly modifiable source that is modulated depending on the current motor context.

Adaptation, Physiological↗

Transient and steady-state dynamics of cortical adaptation.

Adaptation is a ubiquitous property of all sensory pathways of the brain and thus likely critical in the encoding of behaviorally relevant sensory information. Despite evidence identifying specific biophysical mechanisms contributing to sensory adaptation, its functional role in sensory encoding is not well understood, particularly in the natural environment where transient rather than steady-state activity could dominate the neuronal representation. Here, we show that the heterogeneous transient and steady-state adaptation dynamics of single cortical neurons in the rat vibrissa system were well characterized by an underlying state variable. The state was directly predictable from temporal response properties that capture the time course of postexcitatory suppression following an isolated vibrissa deflection. Altering the initial state, by preceding the periodic stimulus with an additional vibrissa deflection, strongly influenced single-cell transient cortical adaptation responses. Despite the different transient activity, neurons reached the same steady-state adapted response with a time to steady state that was independent of the initial state. However, the differences in transient activity observed on small time scales were not present when activity was integrated over the longer time scale of a stimulus cycle. Taken together, the results here demonstrate that although adaptation can have significant effects on transient neuronal activity and direction selectivity, a simple measure of the time course of suppression following an isolated stimulus predicted a large portion of the observed adaptation dynamics.

Action Potentials↗

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.

Action Potentials↗

Forward versus backward walking: transfer of podokinetic adaptation.

We asked whether podokinetic adaptation to walking on a circular treadmill transfers to different forms of locomotion. Subjects were blindfolded and asked to walk straight across the floor, in the forward and backward directions, following podokinetic (PK) stimulation that consisted of 30 min of forward walking-in-place on the perimeter of a disk rotating in the clockwise direction. During both forward and backward walking following forward-walking PK stimulation, subjects involuntarily walked along curved trajectories at angular velocities well above vestibular threshold, although they perceived that they were walking along straight paths. The curved paths of forward and backward walking were indistinguishable from one another. Transfer of PK adaptations acquired during forward walking on the turntable to backward walking trials suggests that the PK system controls general locomotor trajectory. Adaptation of the system thus influences forms of locomotion other than that used during acquisition of the adaptation. This transfer also supports the concept that forward and backward walking are controlled by neural networks that share common elements. An interesting feature of the transfer of PK adaptation is that for both forward and backward walking, subjects turned in a counterclockwise direction. As such, the direction of relative rotation between the trunk and feet was maintained for both forward and backward walking. However, the relationship of the lower extremities to the center of rotation was not preserved. The left limb was the inner leg during PK stimulation and forward walking after adaptation, but the left leg was the outer leg during backward walking. These results suggest that PK adaptation affects general locomotor trajectory via a remodeling of the rotational relationship between the trunk and the feet.

Adaptation, Physiological↗

Towards understanding the process of intestinal adaptation.

When bowel is lost due to disease or surgery, the residual bowel increases its functional capacity in order to compensate for the loss of absorptive capacity. The success and extent of this adaptive process is critical to recovery. This article reviews the current understanding of the intestinal adaptation. Adaptation is a complex process which as yet is poorly understood and thus it is difficult to develop strategies to enhance the out-come of the adaptation phase. Extensive loss of bowel brings about functional as well as morphologic changes in the remaining intestine. The exact relationship between histologic changes and function is still unknown and some studies show that histologic changes may precede functional changes. Both nonnutritive and nutritive factors have been identified as major stimuli to the adaptive process. The importance of oral intake as a positive stimulus has been demonstrated and the role of diet composition rather than diet complexity being recognized. Recent studies attempt to understand the molecular basis of intestinal adaptation by seeking to characterize the nature of humoral factors involved and to establish alterations in the patterns of gene expression. These new approaches may facilitate the identification of both nutritional and pharmacological methods to manipulate the intestinal adaptation process.

Adaptation, Physiological↗

Involvement of capsaicin-sensitive sensory nerves in gastric adaptive relaxation in isolated guinea-pig stomachs.

We investigated the role of capsaicin-sensitive sensory nerves (CPSNs), nitric oxide (NO), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in gastric adaptive and receptive relaxation in isolated guineapig stomachs. Changes in intragastric volume and pressure were recorded simultaneously in isolated stomachs in baths containing atropine and guanethidine. Adaptive relaxation was induced by luminal distention, and receptive relaxation was induced by electrical vagal stimulation. We found that desensitization to capsaicin inhibited adaptive relaxation, but not vagally induced relaxation. Extraluminal capsaicin induced gastric relaxation. Adaptive relaxation and capsaicin-induced relaxation were reduced by both tetrodotoxin and NG-nitro-L-arginine (LNNA), but not by hexamethonium. The effect of LNNA was partially reversed by co-incubation with L-arginine. Neither CGRP(8-37) nor VIP(10-28) inhibited all responses of adaptive relaxation, vagally induced and capsaicin-induced relaxation. These findings suggest that activation of CPSNs may be involved in adaptive relaxation, and that NO, but not CGRP or VIP, may be involved in the mechanisms of adaptive relaxation and receptive relaxation.

Adaptation, Physiological↗