Renal plasticity in response to feeding in the Burmese python, Python molurus bivittatus.

Burmese pythons are sit-and-wait predators that are well adapted to go long periods without food, yet subsequently consume and digest single meals that can exceed their body weight. These large feeding events result in a dramatic alkaline tide that is compensated by a hypoventilatory response that normalizes plasma pH; however, little is known regarding how plasma HCO3(-) is lowered in the days post-feeding. The current study demonstrated that Burmese pythons contain the cellular machinery for renal acid-base compensation and actively remodel the kidney to limit HCO3(-) reabsorption in the post-feeding period. After being fed a 25% body weight meal plasma total CO2 was elevated by 1.5-fold after 1 day, but returned to control concentrations by 4 days post-feeding (d pf). Gene expression analysis was used to verify the presence of carbonic anhydrase (CA) II, IV and XIII, Na(+) H(+) exchanger 3 (NHE3), the Na(+) HCO3(-) co-transporter (NBC) and V-type ATPase. CA IV expression was significantly down-regulated at 3 dpf versus fasted controls. This was supported by activity analysis that showed a significant decrease in the amount of GPI-linked CA activity in isolated kidney membranes at 3 dpf versus fasted controls. In addition, V-type ATPase activity was significantly up-regulated at 3 dpf; no change in gene expression was observed. Both CA II and NHE3 expression was up-regulated at 3 dpf, which may be related to post-prandial ion balance. These results suggest that Burmese pythons actively remodel their kidney after feeding, which would in part benefit renal HCO3(-) clearance.

Divergent Genital Morphologies and Female-Male Covariation in Watersnakes.

Genital evolution can be driven by diverse selective pressures. Across taxa we see evidence of covariation between males and females, as well as divergent genital morphologies between closely related species. Quantitative analyses of morphological changes in coevolving male and female genitalia have not yet been shown in vertebrates. This study uses 2D and 3D geometric morphometrics to quantitatively compare the complex shapes of vaginal pouches and hemipenes across three species of watersnakes (the sister taxa Nerodia fasciata, N. sipedon, and a close relative N. rhombifer) to address the relationship between genital morphology and divergence time in a system where sexual conflict may have driven sexually antagonistic coevolution of genital traits. Our pairwise comparisons of shape differences across species show that the sister species have male and female genitalia that are significantly different from each other, but more similar to each other than to N. rhombifer. We also determine that the main axes of shape variation are the same for males and females, with changes that relate to deeper bilobation of the vaginal pouch and hemipenes. In males, the protrusion of the region of spines at the base of the hemipene trades off with the degree of bilobation, suggesting amelioration of sexual conflict, perhaps driven by changes in the relative size of the entrance of the vaginal pouch that could have made spines less effective.

Characterization of carbonic anhydrase XIII in the erythrocytes of the Burmese python, Python molurus bivittatus.

Carbonic anhydrase (CA) is one of the most abundant proteins found in vertebrate erythrocytes with the majority of species expressing a low activity CA I and high activity CA II. However, several phylogenetic gaps remain in our understanding of the expansion of cytoplasmic CA in vertebrate erythrocytes. In particular, very little is known about isoforms from reptiles. The current study sought to characterize the erythrocyte isoforms from two squamate species, Python molurus and Nerodia rhombifer, which was combined with information from recent genome projects to address this important phylogenetic gap. Obtained sequences grouped closely with CA XIII in phylogenetic analyses. CA II mRNA transcripts were also found in erythrocytes, but found at less than half the levels of CA XIII. Structural analysis suggested similar biochemical activity as the respective mammalian isoforms, with CA XIII being a low activity isoform. Biochemical characterization verified that the majority of CA activity in the erythrocytes was due to a high activity CA II-like isoform; however, titration with copper supported the presence of two CA pools. The CA II-like pool accounted for 90 % of the total activity. To assess potential disparate roles of these isoforms a feeding stress was used to up-regulate CO2 excretion pathways. Significant up-regulation of CA II and the anion exchanger was observed; CA XIII was strongly down-regulated. While these results do not provide insight into the role of CA XIII in the erythrocytes, they do suggest that the presence of two isoforms is not simply a case of physiological redundancy.

Tachykinins (substance P, neurokinin A and neuropeptide gamma) and neurotensin from the intestine of the Burmese python, Python molurus.

Peptides with substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neurotensin-like immunoreactivity were isolated in pure form from an extract of the intestine of the Burmese python (Python molurus). The primary structure of python substance P (Arg-Pro-Arg-Pro-Gln-Gln-Phe-Tyr-Gly-Leu- Met-NH2) shows one amino acid substitution (Phe8-->Tyr) compared with chicken/alligator substance P and an additional substitution (Lys3-->Arg) as compared with mammalian substance P. The neurokinin A-like immunoreactivity was separated into two components. Python neuropeptide gamma (Asp-Ala-Gly-Tyr- Ser-Pro-Leu-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 shows three substitutions (Gly5-->Ser, Gln6-->Pro and Ile7-->Leu) compared with alligator neuropeptide gamma and an additional substitution (His4-->Tyr) compared with mammalian neuropeptide gamma. Python neurokinin A (His-Lys-Thr-Asp-Ser-Phe-Val-Gly- Leu-Met.NH2) is identical to human/chicken/alligator neurokinin A. Python neurotensin (pGlu-Leu-Val-His-Asn-Lys-Ala-Arg-Pro-Tyr-Ile-Leu) is identical to chicken/alligator neurotensin. The data are indicative of differential evolutionary pressure to conserve the amino acid sequences of reptilian gastrointestinal peptides.

Purification and characterization of islet hormones (insulin, glucagon, pancreatic, polypeptide and somatostatin) from the Burmese python, Python molurus.

Insulin was purified from an extract of the pancreas of the Burmese python, Python molurus (Squamata:Serpentes) and its primary structure established as: A Chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Glu-Asn-Thr10-Cys-Ser-Leu-Tyr-Glu-Leu- Glu-Asn-Tyr-Cys20-Asn. B-Chain: Ala-Pro-Asn-Gln-His-Leu-Cys-Gly-Ser-His10-Leu-Val-Glu-Ala-Leu-Tyr- Leu-Val-Cys-Gly20-Asp-Arg-Gly-Phe-Tyr-Tyr-Ser-Pro-Arg-Ser30. With the exception of the conservative substitution Phe --> Tyr at position B25, those residues in human insulin that comprise the receptor-binding and those residues involved in dimer and hexamer formation are fully conserved in python insulin. Python insulin was slightly more potent (1.8-fold) than human insulin in inhibiting the binding of [125I-Tyr-A14] insulin to the soluble full-length recombinant human insulin receptor but was slightly less potent (1.5-fold) than human insulin for inhibiting binding to the secreted extracellular domain of the receptor. The primary structure of python glucagon contains only one amino acid substitution (Ser28 --> Asn) compared with turtle/duck glucagon and python somatostatin is identical to that of mammalian somatostatin-14. In contrast, python pancreatic polypeptide (Arg-Ile-Ala-Pro-Val-Phe-Pro-Gly-Lys-Asp10-Glu-Leu-Ala-Lys-Phe- Tyr20-Thr-Glu-Leu-Gln-Gln-Tyr-Leu-Asn-Ser-Ile30-Asn-Arg-Pro-Arg -Phe.NH2) contains only 35 instead of the customary 36 residues and the amino acid sequence of this peptide has been poorly conserved between reptiles and birds (18 substitutions compared with alligator and 20 substitutions compared with chicken).

Evolution of regulatory responses to feeding in snakes.

Do animal species that normally consume large meals at long intervals evolve to down-regulate their metabolic physiology while fasting and to up-regulate it steeply on feeding? To test this hypothesis, we compared postfeeding regulatory responses in eight snake species: four frequent feeders on small meals and four infrequent feeders on large meals. For each species, we measured factorial changes in metabolic rate, in activities and capacities of five small intestinal brush border nutrient transporters, and in masses of eight organs that function in nutrient processing after consumption of a rodent meal equivalent to 25% of the snake's body mass. It turned out that, compared with frequent feeders, infrequent feeders digest that meal more slowly; have lower metabolic rates, organ masses, and nutrient uptake rates and capacities while fasting; have higher energy expenditure during digestion; and have higher postfeeding factorial increases in metabolic rate, organ masses, and nutrient uptake rates and capacities. These conclusions, which conform to the hypothesis mentioned above, remain after phylogeny has been taken into account. The small organ masses and low nutrient transporter activities during fasting contribute to the low fasting metabolism of infrequent feeders. Quantitative calculations of partial energy budgets suggest that energy savings drive the evolution of low mass and activities of organs during fasting and of large postfeeding regulatory responses in infrequent feeders. We propose further tests of this hypothesis among other snake species and among other ectotherms.

Digestive challenges for vertebrate animals: microbial diversity, cardiorespiratory coupling, and dietary specialization.

The digestive system is the interface between the supply of food for an animal and the demand for energy and nutrients to maintain the body, to grow, and to reproduce. Digestive systems are not morphologically static but rather dynamically respond to changes in the physical and chemical characteristics of the diet and the level of food intake. In this article, we discuss three themes that affect the ability of an animal to alter digestive function in relation to novel substrates and changing food supply: (1) the fermentative digestion in herbivores, (2) the integration of cardiopulmonary and digestive functions, and (3) the evolution of dietary specialization. Herbivores consume, digest, and detoxify complex diets by using a wide variety of enzymes expressed by bacteria, predominantly in the phyla Firmicutes and Bacteroidetes. Carnivores, such as snakes that feed intermittently, sometimes process very large meals that require compensatory adjustments in blood flow, acid secretion, and regulation of acid-base homeostasis. Snakes and birds that specialize in simple diets of prey or nectar retain their ability to digest a wider selection of prey. The digestive system continues to be of interest to comparative physiologists because of its plasticity, both phenotypic and evolutionary, and because of its widespread integration with other physiological systems, including thermoregulation, circulation, ventilation, homeostasis, immunity, and reproduction.

Metabolic and digestive response to food ingestion in a binge-feeding lizard, the Gila monster (Heloderma suspectum).

The gastrointestinal tract possesses the capacity to change in form and function in response to fasting and feeding. Such plasticity can be dramatic for species that naturally experience long episodes of fasting between large meals (e.g. sit-and-wait foraging snakes, estivating anurans). By contrast, for active foraging species that feed more frequently on smaller meals, gastrointestinal responses are more modest in magnitude. The Gila monster Heloderma suspectum is an active foraging lizard that feeds infrequently on meals weighing up to one-third of its body mass. Additionally, Gila monsters possess a species-specific salivary peptide, exendin-4, which may be involved in the regulation of metabolic and digestive performance. To investigate the adaptive postprandial response of Gila monsters and the potential regulatory role of exendin-4, we measured metabolic and intestinal responses to feeding in the presence or absence of circulating exendin-4. Following the consumption of rodent or egg meals equivalent to 10% of lizard body mass, metabolic rates peaked at 4.0- to 4.9-fold of standard metabolic rates and remained elevated for 5-6 days. Specific dynamic action of these meals (43-60 kJ) was 13-18% of total meal energy. Feeding triggered significant increases in mucosal mass, enterocyte width and volume, and the upregulation of D-glucose uptake rates and aminopeptidase-N activity. Total intestinal uptake capacity for L-leucine, L-proline and D-glucose were significantly elevated within 1-3 days after feeding. Whereas the absence of circulating exendin-4 had no impact on postprandial metabolism or the postprandial response of intestinal structure and nutrient uptake, it significantly increased intestinal aminopeptidase-N activity. Within the continuum of physiological responses to feeding and fasting, Gila monsters occupy an intermediate position in experiencing moderate, though significant, regulation of intestinal performance with feeding.

Regulation of digestive performance: a proposed adaptive response.

Among snakes a correlation exists between feeding habits (frequent or infrequent) and the magnitude by which digestive performance is regulated (modest or large). This paper investigates whether the observed regulation of digestive performance is an adaptation to feeding habits and therefore, a product of natural selection. Using data on metabolic and intestinal responses to feeding for amphibians and reptiles, it is attempted to show the selective advantage and independent origin of either modestly or widely regulating gut performance. In an energetic model, snakes that naturally feed frequently on small meals benefit (from lower energy output) from modestly regulating gut performance as opposed to widely regulating gut performance. Likewise, the model suggests an energetic benefit for infrequently-feeding snakes secondary to the wide regulation of gut performance. This benefit is a function of long spans of fasting with a down-regulated gut (thereby incurring a lower standard metabolic rate) and the occasionally incursion of a costly up-regulation of the gut. In a comparison across several distantly-related lineages of amphibians and reptiles, frequently-feeding species all exhibit small postprandial responses in metabolism and intestinal nutrient transport capacities. In contrast, frogs and snakes that routinely fast for long periods independently experience five- to 30-fold increases in metabolism and intestinal performance with feeding. Among amphibians and reptiles the evidence presented supports the hypothesis that the extent by which the gut is regulated is an adaptive trait that evolved with divergence in feeding habits and energy budgets. In finishing, the foundations, caveats, and suggested future tests of this adaptive hypothesis are presented.

Specific dynamic action of a large carnivorous lizard, Varanus albigularis.

Varanus albigularis inhabits grasslands of southern and eastern Africa and experiences months of fasting during the dry season (May-December) followed by voracious feeding during the wet season (January-April). Previous studies have found that sit-and-wait foraging snakes, which also experience long intervals between large meals, exhibit unprecedented increases in post-feeding metabolism, which reflects the added cost of up-regulating a previously quiescent gut and digesting a large meal. Hence we measured pre- and post-prandial oxygen consumption rates (VO2) of adult V. albigularis in order to observe whether they exhibit similarly large metabolic responses to digestion as sit-and-wait foraging snakes. Following the consumption of meals consisting of ground turkey and snails, hard-boiled eggs, or juvenile rats, lizards rapidly increased their VO2 to peak within 24-27 hr at 7-10 times pre-feeding values (mean = 0.035 mL O2.g-1.h-1). During the 60-90 hr of significantly elevated VO2, the extra oxygen consumed (the specific dynamic action) represented an energy expenditure of 830-1260 kJ. For meals that were fully digested, specific dynamic action equalled 24% of ingested energy. The magnitudes of V. albigularis post-prandial metabolic responses are similar to those previously observed for sit-and-wait foraging snakes. Like sit-and-wait foraging snakes, V. albigularis may also down-regulate intestinal performance during their months of fasting (suggested by their relatively low standard metabolic rate) and then up-regulate their gut (bearing its high energetic cost) upon feeding.

Determinants of the postfeeding metabolic response of Burmese pythons, Python molurus.

The relatively large meal sizes consumed by sit-and-wait-foraging snake species make them favorable for investigating specific dynamic action, the rise in metabolic rate associated with digestion. Hence, we measured O2 consumption rates (VO2) before and up to 20 d after Burmese pythons (Python molurus) either had only constricted and killed rodent meals or had also been allowed to consume meals ranging in size from 5% to 111% of their body mass. Postprandial VO2 peaked within 2 d at a value that increased with meal size, up to 44 times standard metabolic rate for the largest meals. In addition to being the largest known magnitude of postprandial metabolic response, this also exceeds the factorial increase in VO2 during peak physical activity for all studied animals except perhaps racehorses. Specific dynamic action, calculated from the extra VO2 above standard metabolic rate over the duration of digestion, increased with meal size and equaled 32% of ingested meal energy. The allometric exponent for body mass was 0.68 for standard metabolic rate, 0.90 for peak postprandial VO2, and 1.01 for specific dynamic action. Specific dynamic action is higher, and standard metabolic rate is lower, in sit-and-wait-foraging snake species than in actively foraging snake species. This suggests that sit-and-wait-foraging snakes, which consume large meals at long and unpredictable intervals, reduce standard metabolic rate by allowing the energetically expensive small intestine and other associated organs to atrophy between meals but thereby incur a large specific dynamic action while rebuilding those organs upon feeding.

Effects of meal size on postprandial responses in juvenile Burmese pythons (Python molurus).

Pythons were reported previously to exhibit large changes in intestinal mass and transporter activities on consuming meals equal to 25% of the snake's body mass. This paper examines how those and other adaptive responses to feeding vary with meal size (5, 25, or 65% of body mass). Larger meals took longer to pass through the stomach and small intestine. After ingestion of a meal, O2 consumption rates rose to up to 32 times fasting levels and remained significantly elevated for up to 13 days. This specific dynamic action equaled 29-36% of ingested energy. After 25 and 65% size meals, plasma Cl- significantly dropped, whereas plasma CO2, glucose, creatinine, and urea nitrogen increased as much as a factor of 2.3-4.2. Within 1 day the intestinal mucosal mass more than doubled, and masses of the intestinal serosa, liver, stomach, pancreas, and kidneys also increased. Intestinal uptake rates of amino acids and of D-glucose increased by up to 43 times fasting levels, whereas uptake capacities increased by up to 59 times fasting levels. Magnitudes of many of these responses (O2 consumption rate, kidney hypertrophy, and D-glucose and L-lysine uptake) increased with meal size up to the largest meals studied; other responses (Na+-independent L-leucine uptake, plasma Cl-, and organ masses) plateaued at meals equal to 25% of the snake's body mass; and still other responses (nutrient uptake at day 1, passive glucose uptake, and plasma protein and alkaline phosphatase) were all-or-nothing, being independent of meal size between 5 and 65% of body mass. Pythons undergo a wide array of postprandial responses, many of which differ in their sensitivity to meal size.

Adaptive responses to feeding in Burmese pythons: pay before pumping.

Burmese pythons normally consume large meals after long intervals. We measured gut contents, O2 consumption rates, small intestinal brush-border uptake rates of amino acids and glucose, organ masses and blood chemistry in pythons during the 30 days following ingestion of meals equivalent to 25% of their body mass. Within 1-3 days after ingestion, O2 consumption rates, intestinal nutrient uptake rates and uptake capacities peaked at 17, 6-26 and 11-24 times fasting levels, respectively. Small intestinal mass doubled, and other organs also increased in mass. Changes in blood chemistry included a 78% decline in PO2 and a large 'alkaline tide' associated with gastric acid section (i.e. a rise in blood pH and HCO3- concentrations and a fall in Cl- concentration). All of these values returned to fasting levels by the time of defecation at 8-14 days. The response of O2 consumption (referred to as specific dynamic action, SDA) is the largest, and the upregulation of intestinal nutrient transporters the second largest, response reported for any vertebrate upon feeding. The SDA is a large as the factorial rise in O2 consumption measured in mammalian sprinters and is sustained for much longer. The extra energy expended for digestion is equivalent to 32% of the meal's energy yield, with much of it being measured before the prey energy was absorbed.

A vertebrate model of extreme physiological regulation.

Investigation of vertebrate regulatory biology is restricted by the modest response amplitudes in mammalian model species that derive from a lifestyle of frequent small meals. By contrast, ambush-hunting snakes eat huge meals after long intervals. In juvenile pythons during feeding, there are large and rapid increases in metabolism and secretion, in the activation of enzymes and transporter proteins, and in tissue growth. These responses enable an economic hypothesis concerning the evolution of regulation to be tested. Combined with other experimental advantages, these features recommend juvenile pythons as the equivalent of a squid axon in vertebrate regulatory biology.

Ventilatory and cardiovascular responses of a python (Python molurus) to exercise and digestion.

To investigate the potential limiting steps of peak metabolic rates, we examined gas exchange rates ( vdot (O2), vdot (CO2)), respiratory exchange ratio (RER), breathing frequency, tidal volume, minute ventilation volume (V.e) as well as the heart rate, systemic blood flow and stroke volume of Burmese pythons (Python molurus) while fasting at rest, exercising, digesting and exercising while digesting. All measured variables increased significantly during exercise (crawling at 0.4 km h(-)(1) and at vdot (O2max)), highlighted by a 17-fold increase in vdot (CO2) and a 24-fold increase in V.e. During the digestion of a meal equivalent to 25 % of the snake's body mass, pythons responded with increases in vdot (O2) and heart rate similar to those experienced during exercise, along with a 4.5-fold increase in systemic blood flow. Interestingly, pythons hyperventilated while exercising, whereas they hypoventilated during digestion. The combined demands of exercise and digestion resulted in significantly higher vdot (O2), vdot (CO2), breathing frequency and heart rate than during either exercise or digestion alone. Evidently, the capacities of the ventilatory and cardiovascular systems to transport oxygen to locomotor muscles are not a limiting factor in the attainment of peak metabolic rates during exercise in pythons

Rapid upregulation of snake intestine in response to feeding: a new model of intestinal adaptation.

Mammalian guts exhibit numerous adaptive responses to feeding. However, response magnitudes are often inconveniently modest for experimental analysis, because mammals feed often and their intestines are rarely empty. We anticipated larger responses in sit-and-wait foraging snakes, because they consume huge meals at long intervals. Hence, we studied metabolic rates, brush-border nutrient transport, and intestinal morphometrics in the rattlesnake, Crotalus cerastes, as a function of time since feeding. O2 consumption by the whole snake, a reflection of the cost of digestion and of rebuilding the starved gut, peaked after 2 days at eight times fasting values. Activities of brush-border glucose, leucine, and proline transporters peaked after 1-3 days at 5-22 times fasting values. Ratios of amino acid to glucose uptake rates peaked at 104, reflecting snakes' extreme adaptation to carnivory (a high-protein low-carbohydrate diet). Intestinal mass increased more than twofold within 1 day, primarily because of mucosal growth. After defecation, the intestine atrophied, brush-border transporters were downregulated, and O2 consumption returned to basal. These rapid and large responses reduce costs of gut maintenance during long bouts of quiescence between meals. Hence sit-and-wait foraging snakes may furnish advantageous model species for studying gut regulation and adaptation.

Insulin and proglucagon-derived peptides from the horned frog, Ceratophrys ornata (Anura:Leptodactylidae).

Insulin and peptides derived from the processing of proglucagon have been isolated from an extract of the pancreas of the South American horned frog, Ceratophrys ornata (Leptodactylidae). Ceratophrys insulin is identical to the insulin previously isolated from the toad, Bufo marinus (Bufonidae). Ceratophrys glucagon was isolated in two molecular forms with 29- and 36-amino acid residues in approximately equal amounts. Glucagon-29 is identical to glucagon from B. marinus and from the bullfrog, Rana catesbeiana (Ranidae) and contains only 1 amino acid substitution (Thr29 --> Ser) compared with glucagon from Xenopus laevis (Pipidae). Glucagon-36 comprises glucagon-29 extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Met-Ser. This extension is structurally dissimilar to the C-terminal octapeptide of mammalian oxyntomodulin and resembles more closely that found in C-terminally extended glucagons isolated from fish pancreata. Ceratophrys glucagon-like peptide-1 (GLP-1) (His-Ala-Asp-Gly-Thr-Tyr-Gln-Asn-Asp-Val10-Gln-Gln-Phe-Leu-Glu- Glu-Lys-Ala-Ala-Lys20-Glu-Phe-Ile-Asp-Trp-Leu-Ile-Lys-Gly- Lys30-Pro-Lys-Lys-Gln-Arg-Leu-Ser) contains 3 amino acid substitutions compared with the corresponding peptide from B. marinus, 8 substitutions compared with GLP-1 from R. catesbeiana, and between 4 and 11 substitutions compared with the three GLP-1 peptides identified in X. laevis proglucagon. GLP-2 was not identified in the extract of Ceratophrys pancreas. The data indicate that, despite its importance in the regulation of glucose metabolism, the primary structure of GLP-1 has been very poorly conserved during evolution, even among a single order such as the Anura.

Responses of python gastrointestinal regulatory peptides to feeding.

In the Burmese python (Python molurus), the rapid up-regulation of gastrointestinal (GI) function and morphology after feeding, and subsequent down-regulation on completing digestion, are expected to be mediated by GI hormones and neuropeptides. Hence, we examined postfeeding changes in plasma and tissue concentrations of 11 GI hormones and neuropeptides in the python. Circulating levels of cholecystokinin (CCK), glucose-dependent insulinotropic peptide (GIP), glucagon, and neurotensin increase by respective factors of 25-, 6-, 6-, and 3.3-fold within 24 h after feeding. In digesting pythons, the regulatory peptides neurotensin, somatostatin, motilin, and vasoactive intestinal peptide occur largely in the stomach, GIP and glucagon in the pancreas, and CCK and substance P in the small intestine. Tissue concentrations of CCK, GIP, and neurotensin decline with feeding. Tissue distributions and molecular forms (as determined by gel-permeation chromatography) of many python GI peptides are similar or identical to those of their mammalian counterparts. The postfeeding release of GI peptides from tissues, and their concurrent rise in plasma concentrations, suggests that they play a role in regulating python-digestive responses. These large postfeeding responses, and similarities of peptide structure with mammals, make pythons an attractive model for studying GI peptides.

Luminal and systemic signals trigger intestinal adaptation in the juvenile python.

Juvenile pythons undergo large rapid upregulation of intestinal mass and intestinal transporter activities upon feeding. Because it is also easy to do surgery on pythons and to maintain them in the laboratory, we used a python model to examine signals and agents for intestinal adaptation. We surgically isolated the middle third of the small intestine from enteric continuity, leaving its mesenteric nerve and vascular supply intact. Intestinal continuity was restored by an end-to-end anastomosis between the proximal and distal thirds. Within 24 h of the snake's feeding, the reanastomosed proximal and distal segments (receiving luminal nutrients) had upregulated amino acid and glucose uptakes by up to 15-fold, had doubled intestinal mass, and thereby soon achieved total nutrient uptake capacities equal to those of the normal fed full-length intestine. At this time, however, the isolated middle segment, receiving no luminal nutrients, experienced no changes from the fasted state in either nutrient uptakes or in morphology. By 3 days postfeeding, the isolated middle segment had upregulated nutrient uptakes to the same levels as the reanastomosed proximal and distal segments, but it still lacked any appreciable morphological response. These contrasting results for the reanastomosed intestine and for the isolated middle segment suggest that luminal nutrients and/or pancreatic biliary secretions are the agents triggering rapid upregulation of transporters and of intestinal mass and that systemic nerve or hormonal signals later trigger transporter regulation but no trophic response.