Showing papers in "Experimental Biology and Medicine in 1975"

Changes in blood hormone levels during the immune response.

Abstract: Injection of three different antigens into rats or mice led in the course of several days to about a threefold increase in serum corticosterone levels and concommitantly to a decrease in thyroxine (rats). In view of the known immuno-suppressive effect of the glucocorticoids the possibility is considered that the endocrine changes induced during the immune response could significantly modulate the subsequent character of the immune response, e.i. magnitude, duration and lymphoid cell proliferation, however, a more complete pattern of hormonal variations and their cause needs to be established. These findings while admittedly preliminary, suffice to provide an indication of a temporal pattern of hormonal change during the immune response which could be important in immunoregulation.

Radioimmunoassay for GH-release inhibiting hormone.

Abstract: The synthetic growth hormone release inhibiting hormone (GH-RIH) was conjugated with human serum globulin using glutaraldehyde and administered to rabbits. An antiserum thus generated 70% of 125I-Tyr1-GH-RIH. The binding was inhibited by unlabelled GH-RIH and the inhibition was dose-related, enabling us to establish a radioimmunoassay method for GH-RIH. The minimum detectable dose was 4 pg. A linearity was demonstrated for immunoreactive GH-RIH of extracts of rat and pig hypothalami, indicating that they contained substance(s) indistinguishable from GH-RIH. Various hypothalamic and pituitary hormones did not interfere with the radioimmunoassay, but considerable cross-reaction was observed for linear GH-RIH and the ring portion of GIH-RIH, suggesting that the antigenic determinant involved the amino acid sequence from position 3-14 of GH-RIH or part of it. Plasma protein appears to contain substance(s) immunologically indistinguishable from GH-RIH or to interfere, in a nonspecific manner, with the radioimmunoassay system for GH-RIH.

Fetal bovine serum: a multivariate standard.

Abstract: SummaryChemical and endocrine parameters were investigated in commercially available fetal bovine sera intended for use as culture media supplements. A high degree of serum variability was present both within and between suppliers in all major categories investigated. It is suggested that caution be employed in the interpretation of results from experiments utilizing serum supplements without specific quantitation of possible interfering or modulating factors.The authors thank Dr. H. A. Tucker for the bovine growth hormone and bovine prolactin RIA and Dr. P. Foa for the total and pancreatic glucagon RIA.

25-Hydroxyvitamin D3: Evidence of an Enterohepatic Circulation in Man

Abstract: SummaryWithin 24 hr after intravenous administration of isotopic 25-hydroxyvitamin D3 to three normal adults for kinetic studies, one-third of the radioactivity was secreted into the lumen of the duodenum, probably with the bile. The subsequent intestinal reabsorption of over 85% of secreted radioactivity suggests that this major metabolite of vitamin D has a hitherto unrecognized enterohepatic circulation.Our observation of a dynamic hepatic secretion and intestinal reabsorption of radioactivity administered as 3H-labeled 25-hydroxyvitamin D3 to vitamin D-replete man is indicative of an enterohepatic circulation that may be of physiologic importance. It is conceivable that interruption in the recycling of 25-OH-D3 may be an important mechanism of acquired deficiency of vitamin D in gastrointestinal disease.This investigation was supported in part by Research Grants AM-69-2168, RR 585, and AM-6908 from the National Institutes of Health, Public Health Service. We gratefully acknowledge the technical assist...

Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations.

Abstract: A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.

Sodium Urate Accelerates Precipitation of Calcium Oxalate In Vitro

Abstract: Precipitation of calcium oxalate crystals from a metastable solution can be detected within 10 min if crystalline sodium urate is added at a solid to liquid ratio of 0.1 mM or more. Without urate, precipitation begins after 50 min. Uric acid is not effective. Pyrophosphate inhibits the effects of sodium urate.

Levels of lutenizing hormone, estradiol and progesterone in serum during the estrous cycle and pregnancy in the beagle bitch (38491).

Abstract: Levels of luteinizing hormone (LH), estradiol-17 beta and progesterone were determined by specific radioimmunoassays in sera obtained from Beagle bitches during proestrus, estrus and diestrus. Concentrations of LH (expressed as NIH-LH-SI equivalents) were 2.8 plus or minus 0.1 ng/ml in proestrus, 35.5 plus or minus 10.0 ng/ml during early estrus and 2.2 plus or minus 0.1 ng/ml in early diestrus. Peak levels of estradiol-17beta (68.9 plus or minus 11.0 ng/ml) were detected 24 hr prior to the LH peak, declined rapidly and reached basal levels (17.8 plus or minus 6.3 ng/ml) by five days following the LH peak. Levels of progesterone were 1.7 plus or minus 0.3 ng/ml during proestrus, 3.5 plus or minus 0.3 ng/ml during early estrus and 23.3 plus or minus 2.8 ng/ml on day 5 after the LH peak . Progesterone levels remained elevated through day 28 of diestrus and pregnancy. A significant decrease (p smaller than 0.05) in levels of prosgesterone occurred between day 28 of pregnancy and one day prior to shelping (3.3 plus or minus 1.2 ng/ml, with a further decrease on the day of whelping (1.1 plus or minus 0.2 ng/ml). Levels of estradiol-17beta and LH did not change significantly (p smaller than 0.0k) during diestrus or pregnancy.

Heterogeneous Nucleation of Calcium Oxalate by Seeds of Monosodium Urate

Abstract: SummarySeeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria.This work was supported by a Grant from the USPHS (R01-AM16061) and by a Grant from Burroughs-Wellcome Co.

Physical, chemical, and morphologic dimensions of human hepatitis. A virus strain CR326

Abstract: CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 nm spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, indentical 27 nm viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The bouyant density of the virus in CsCl was 1.34 and it was heat (60 degrees), ether and acid stable but was destroyed by heat (100 degrees), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.

Factors involved in the intestinal feedback regulation of pancreatic enzyme secretion in the rat.

Abstract: Further studies on the feedback regulation of pancreatic enzyme secretion by trypsin were conducted in conscious rats, surgically prepared so that pancreatic juice could be collected or returned. Suppression of enzyme secretion by trypsin as well as its stimulation by SBTI occurred only in the upper part of the small intestine, where the hormone CCK is known to be released. Over a limited range, trypsin suppression of pancreatic secretion was proportional to the dose of trypsin. Higher concentrations had no further effect, suggesting "saturation" of the intestine. Trypsin which had its active center blocked by DFP did not suppress enzyme output. These results supported the concept that only trypsin (or chymotrypsin) with an exposed active center suppressed pancreatic enzyme secretion in the rat by somehow suppressing the release of CCK from the intestinal cell. Presumably CCK is released from the intestine following "removal" of trypsin from the intestine either by diverting the juice or by feeding SBTI which binds the enzyme. All of the evidence supported the view that the effect of trypsin or SBTI on pancreatic secretion was mediated at the intestinal level and not in the blood as has been suggested.

Renin release, an artifact of anesthesia and its implications in rats.

Abstract: In our attempt to find an anesthetic agent which did not influence the renin-angiotensin system in the rat, the effect of widely used injectable and gaseous anesthetics and narcotic agents on renin release was chacterized. All of the agents studied induced dose- and time-related increases in serum renin activity when administered in anesthetic doses. Preliminary experiments in anesthetic doses. Preliminary experiments indicated that cardiovascular effects were highly variable, giving little insight into the relationship between renin release and cardiovascular changes. Propranolol impaired most of the anesthesia-induced renin release and impaired aldosterone release with the one agent (urethane) studied. Renin release by two anesthetic agents (ketamine and urethane) appeared to be mediated premarily through the beta-adrenermediated primarily through the beta-adrenergic receptor mechanism, but equivocal results were obtained with other agents (pentobarbital and morphine). It is possible that other anesthetics, as with urethane, may induce aldosterone release by way of renin release. This anesthesia-induced renin release and the extensive biologic activities of angiotensin and aldosterone suggest a potential for influencing many investigations, particularly those involving cardiovascular and endocrine systems.

Influence of lead and cadmium on the susceptibility of rats to bacterial challenge.

Abstract: Intravenous administration of an acute dose of lead acetate or cadmium acetate enhanced the susceptibility of rats to intravenous challenge with E. coli by approximately 1000-fold. Since equivalent vulnerability of lead- or cadmium-treated rats to killed E. coli was observed, toxicity is probably due to the endotoxin content of the bacteria. This postulate is further supported by the observation that equal doses of the Gram-positive bacteria, Staphylococci epidermidis, failed to elicit lethality in the acute lead-intoxicated rats. The synthetic glucocorticoid, methylprednisolone, prevented lethality induced by the Gram-negative bacteria in lead-treated rats. It did not, however, afford significant protection in cadmium-treated rats in the presence of E. coli. Marked alterations in hepatic morphology were apparent in both lead- and cadmium-treated rats challenged with E. coli.

A specific complement-fixation test for human hepatitis a employing CR326 virus antigen. Diagnosis and epidemiology.

Abstract: A specific diagnostic complement-fixation test for hepatitis A antibody in human serum was described employing livers of marmosets infected with CR326 strain human hepatitis A virus Persons with hepatitis A, but not hepatitis B, developed hepatitis A CF antibody shortly after the onset of illness and this persisted thereafter Good agreement was noted in the development of CF and neutralizing antibodies in hepatitis A cases Hepatitis A was shown to occur in a person with hepatitis B antigenemia and hepatitis B occurred in persons with hepatitis A antibody Most persons with hepatitis A who were tested, but none of those with hepatitis B, developed increased anticomplementary activity in their sera at the time of onset of illness At least one patient with hepatitis A developed antibody against normal liver that persisted The possible inplications of this in relation to pathogenesis and to non-specific diagnostic tests in hepatitis were discussed A limited epidemiologic study of a family outbreak of hepatitis in Costa Rica and of a group of young adults in our epidemic country acquire their infections at an early age and are immune thereafter; persons in areas of relatively low incidence may proceed into adulthood without experience with hepatitis A The CF test should provide an excellent tool for diagnosis and for epidemiologic investigation of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture

Interferon crosses blood-cerebrospinal fluid barrier in monkeys.

Abstract: SummaryInterferon was detected in the cerebrospinal fluid (CSF) of monkeys injected iv or im with 30 million units of human leukocyte interferon. The im injection maintained a long-lasting plateau at about l/30th of the corresponding level of interferon in the serum. Interferon injected into the cerebrospinal canal was cleared from CSF at a similar rate as it disappeared from blood after iv administration of a high dose. A relatively stable serum level was maintained for 12-24 hr after the injection of interferon into the CSF space.

Greater number of capillary endothelial cell mitochondria in brain than in muscle.

Abstract: The selective permeability of the brain mircrocirculatory bed (the blood-brain barrier-BBB) is widely believed to have its locus at the brain capillary endothelial cell. Whereas capillaries in other tissue are nonspecifically permeable to all small molecules by virtue of open clefts between endothelial cells, cellular fenestrae and pino-cytosis, these nonspecific routes of exchange are virtually absent in brain, and transcapil-lary exchange probably takes place through the membranous walls and the cytoplasm of endothelial cells. Although most organic molecular exchange is probably bidirectional and net flux is determined by concentration gradients, recent studies have suggested a unidirectional flux out of the brain for potassium, iodide and organic anions (1-3). Such uphill unidirectional transport would require a source of energy in the brain capillary endothelial cell.If the brain capillary wall performs an energy-dependent excretory function as a substantial part of its total metabolic work, it might ...

Calcium-binding protein: its cellular localization in jejunum, kidney and pancreas.

Abstract: Calcium-binding protein (CaBP) was localized with peroxidase-labeled antibody in human jejunum and kidney, and in kidney and pacreas of several animal species. The protein was associated with plasma membrane and intercellular space of jejunal absorptive cells. It was present in a specific population of renal tubule cells and in pancreatic islet cells. Immunohistochemical staining of intestinal CaBP with antibody to renal CaBP indicates structural similarity between the two proteins despite their different molecular weight.

Influence of vitamin E on platelet aggregation and thrombocythemia in the rat.

Abstract: Collagen-induced platelet aggregation was increased in 9-10 wk old vitamin E deficient rats although there was no difference in platelet count between deficient and control animals. With a more prolonged deficiency (at 15 wk) both platelet aggregation and platelet counts were elevated in the vitamin E deficient animals.

Prevention of hereditary cardiomyopathy in the hamster by verapamil and other agents.

Abstract: Verapamil, Prenylamine and, to a lesser extent, Cinnarizine were highly efficient in preventing the development or reducing the severity of heart lesions in cardiomyopathic hamster of the UM-X7.1 line. The calcium antagonistic compounds did not protect against the skeletal muscle changes already present at the time when treatment was initiated. The cardiac lesions were also significantly diminished in frequency and severity by a low calcium diet and in apparent contradiction, by parenteral administration of calcium gluconate. The relation of these electrolytes and creatine phosphokinase is not yet fully understood but suggests that a primary defect in muscles cell membranes may be responsible for hereditary cardiomyopathy in hamsters.

The role of c3 as an opsonin in the early stages of infection.

Abstract: In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically deficient in C5, were depleted of serum C3 by the injection of purified cobra venom factor (CoVF). Concurrent with their C3 depletion, their serum opsonizing activity decreased to a level less than 20% of normal. When these mice were challenged with an intraperitoneal injection of pneumococci 2 hr after the CoVF treatment, the LD50 was from 30 to 80 times lower than the LD50 in saline-treated control animals. When the CoVF was given only 6 hr after the pneumococcal challenge, the LD50 was the same as in the control mice. If the pneumococci were first preopsonized in vitro and then injected into CoVF-treated animals, the LD50 was the same as that in control animals. These experiments demonstrate that C3 plays a significant role in vivo in the host's defense against infection and that a major part of that role is through its action as an opsonin. Furthermore, these experiments demonstrate that the role of C3 is most significant during the early stages of bacterial invasion.

Teratogenic effects of cyclopamine and jervine in rats, mice and hamsters.

Abstract: SummaryGolden hamster fetuses were extremely sensitive to the teratogenic action of jervine and cyclopamine, the steroidal alkaloid teratogens from Veratrum cali-fornicum. Cebocephaly, harelip/cleft palate, exencephaly, and a cranial bleb were the common deformities produced by dosing on the seventh day of gestation. Sprague-Dawley derived albino rats were susceptible to cyclopamine but not to jervine, and at an incidence very much lower than that of hamsters. Cebocephaly and microphthalmia were the common deformities. The terata were observed as a consequence of sixth-to ninth-day dosings. Single-day dosing produced no terata. Swiss Webster mice were apparently resistant to the teratogens.

Superoxide Dismutase Activity in Copper-Deficient Swine

Abstract: SummaryThese experiments demonstrate the dependency of cuprozinc superoxide dismutase activity in red cells and liver on an adequate dietary intake of copper. The superoxide dismutase activity in red cells decreased to 15% of control values and, therefore, these cells may be used as a convenient model for studying the physiologic consequences of free radicals.The authors are grateful for the technical assistance of Mr. George Trappett, Mr. Dale Chlarson, Ms. Jacqueline E. Thomas, and Mrs. Alice W. Tustison.

Levels of prostaglandin F (PGF) in bovine endometrium uterine venous, ovarian arterial and jugular plasma during the estrous cycle (38789).

Abstract: Prostaglandins F (PGF) were measured in uterine vein, ovarian artery, and jugular vein plasma and in the endometrial tissues at various times during the bovine estrous cycle, and were compared to peripheral plasma progesterone levels. Four groups of heifers at days 1-5, 10-14, 15-17 and 20-0 of the estrous cycle were studied. Low levels of PGF (48 plus or minus 12 ng/g dry tissue were measured in the endometrium on days 1-14 of the cycle. Higher values (131 plus or minus 9.0) were found at days 15 until the day of estrus (p less than 0.001). Similarly, very low levels of PGF were observed in the uterine vein plasma at days 1-14 (0.162) plus or minus 0.044) ng/mlM plus or minus S.E.), whereas on days 15 until the day of estrus the levels ranged from 1.5 to 3.0 ng/ml. The increases in uterine vein PGF on day 15 occurred even while peripheral plasma progesterone levels were still high. However, PGF was not elevated in either the ovarian artery or the jugular vein at any time during the cycle, even when uterine vein levels were greatly elevated. No differences in PGF content were detected in endometrial tissue from uterine horns adjacent or opposite to the functional corpus luteum.

High dietary fat, elevation of rat serum prolactin and mammary cancer.

Abstract: In a previous communication (1) we reported that 7,12-dimethylbenz (a) anthracene (DMBA)-treated rats fed a 20% fat semisynthetic diet exhibited a higher mean mammary tumor incidence (56%) than rats fed a 0.5% fat diet (34%), thus confirming the earlier studies of Carroll and coworkers (2, 3). Also, on the basis of experiments using hormone antagonists we tentatively concluded that the high fat effect was mediated through elevated serum prolactin and that changes in the estrogen-receptor system were probably not involved.We now submit direct evidence, based on the radioimmunoassay of serum prolactin, that animals maintained on high-fat diets (HF) exhibit significantly higher serum prolactin levels during the proestrus-estrus period than animals fed low fat diets (LF).Materials and Methods. Forty virgin female Sprague-Dawley rats (ARS/Sprague-Dawley, Madison, WI) were housed five in a cage in a temperature (24° ± 1°), humidity (50%) and light controlled (12 hr/ day) room and fed Purina Lab Chow and water a...

Effect of dietary Ca and Cd level of pregnant rats on reproduction and on dam and progeny tissue mineral concentrations.

Abstract: The effects of the addition of 220 ppm of dietary cadmium (Cd) and calcium (Ca) (.07% and .96%) on reproduction and mineral concentrations were studied in pregnant rats and their progeny. The addition of Cd significantly reduced feed consumption and body weight gain (p less than .01) while both levels of Ca had no such effect. Liver and kidney Cd levels were significantly higher in the presence of low Ca than with high Ca (p less than .01). Dietary Cd also significantly increased liver zinc content (p less than .01) and decreased liver iron content (p less than .1). The average number of pups per litter was slightly but not significantly less in the Cd group though the average weight at birth was significantly less (p less than .01). Progeny concentrations of zinc copper and iron were significantly decreased and Ca concentrations were significantly increased with the Cd diet (p less than .01). The difference between high and low Ca diet on pup Cd content was significant (p less than .05). The biological importance of the alteration in maternal and fetal concentrations of zinc copper and iron by the supplementation of Cd in maternal diets is not known.

Effects of indomethacin on local blood flow regulation in canine heart and kidney.

Abstract: In two series of experiments we studied the effects of indomethacin on (a) coronary reactive hyperemia and, (b) renal blood flow, autoregulation, and reactive dilation. Coronary blood flow was measured in closed-chest dogs. Reactive hyperemia was induced by coronary occlusion for 5 and 15 sec. Indomethacin, an inhibitor of prostaglandin synthesis, was infused intra-arterially in doses of 90-200 mg over periods ranging from 30-120 min. Coronary reactive hyperemia was not affected by indomethacin. The canine renal vascular bed was studied under conditions of natural flow, controlled flow, and controlled pressure. Intra-arterial infusion of 90 mg of indomethacin over a 30- to 60- min period caused increased renal vascular resistance and an attenuation of reactive dilation (induced by stopping renal blood flow for 90 sec). Indomethacin slightly attenuated the autoregulatory response to decreasing perfusion pressures, but did not affect the respone to increasing pressures. Thus the study fails to provide evidence for participation of the prostaglandins in regulation of coronary blood flow and suggests only minimal participation of prostaglandings in renal blood flow regulation.

Effect of force-feeding upon basal insulin levels of rats.

Abstract: Rats were over- or under-fed to achieve a wide range of body weights. The effect of this treatment on basal insulin levels, with and without pretreatment with atropine, was examined. Basal insulin was positively correlated with body weight and this relationship was essentially unchanged in the presence of atropine.

Injectable Selenium: Effect on the Primary Immune Response of Mice

Abstract: SummarySodium selenite administered to mice ip (ca. 5 μg Se) enhances the primary immune response to the sheep red blood cell antigen. Enhancement of the primary immune response is greatest when Se is administered prior to or simultaneously with the sheep red blood cell antigen.

Myocardial extraction of labeled long-chain fatty acid analogs (38509).

Abstract: SummaryThe single circulation myocardial extraction of terminally iodinated hexadecenoic acid (77 ± 11.0%) is approximately two times the extraction of 18 carbon fatty acids (33 ± 5.2%) prepared by iodination of double bonds. The results compare favorably with natural 18 carbon stearic (70 ± 7.5%) and oleic (61 ± 7.8%) acids labeled with carbon-11 in the carboxyl group. It is concluded that terminally radioiodinated long chain fatty acids can be used as substitutes for in vivo investigations of fatty acid distribution and in particular may be useful as a regional myocardial blood flow indicator.The authors are indebted to Mrs. Alice Lee, Mr. Carl Selin, and Mr. Joe Takahashi for technical assistance.

Serum prolactin levels and prolactin binding activity in adrenals and kidneys of male rats after dehydration, salt loading, and unilateral nephrectomy.

Abstract: SummarySerum prolactin (PRL) levels and PRL binding activity in microsomal membranes from kidneys and adrenals were measured in control, water-deprived, unilaterally nephrectomized, and salt-loaded male rats. Unilateral nephrectomy and water deprivation increased serum prolactin levels significanty. Unilateral nephrectomy did not alter PRL binding activity in the kidneys, but significantly increased it in the adrenal glands. Salt loading had no effect on serum prolactin levels or PRL binding in the kidneys, but significantly increased PRL binding in the adrenal glands. Inhibition curves and tests of cross reactivity with LH, FSH, TSH, and GH showed that binding of PRL to its receptors in the kidneys and adrenals was specific. These observations suggest that PRL has a role in salt and water metabolism and that PRL receptors in the kidney and adrenals participate in this regulatory system.

Relationship of blood concentrations of calcium, phosphate, gastrin and calcitonin to the onset of feeding in the rat.

Abstract: Daily fluctuations in plasma calcium concentrations in rats trained to a closely regulated feeding pattern have been compared to corresponding plasma gastrin and calcitonin concentrations. The time period studied was that extending from 4 hr prior to the start of the feeding. Both plasma calcium and phosphate levels fedd prior to the start of the feeding period and remained low at least for the first 2 hr of feeding. This pattern was also observed in rats in which food was withheld for 2 hr past the regular feeding time. Plasma 45Ca and 32P concentrations (radionuclide injected at least one week prior to sampling) did not follow the pattern of their stable counterparts. Instead, these values rose or remained constant until after feeding had commenced, after which they fell precipitously. Both plasma calcitonin and gastrin levels rose rapidly after the start of the feeding period. The primary point of emphasis is that calcitonin secretion was produced in these rats by an intestinal related stimulus and not by a rise in plasma calcium concentration.