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C W Cooper

Publications and source records attributed to C W Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1983

Calcitonin depresses amphetamine-induced locomotor activity.

Synthetic salmon calcitonin (sCT), given subcutaneously (6.4 micrograms/kg) or intracerebroventricularly (ICV, 30-600 ng), depressed amphetamine-induced locomotor activity in rats by more than 50%. ICV injection of sCT, either three hours or immediately before intraperitoneal amphetamine (1-3 mg/kg), significantly reduced the amphetamine-induced activity. In the absence of amphetamine, sCT had no effect on locomotor activity during the first 100 minutes after treatment. These results show sCT can act centrally to modify drug-induced behavior and may be related to reports of calcitonin receptors and calcitonin-like peptides in the brain.

Animals↗
PubMed1983

Secretion of calcitonin in the genetically obese Zucker rat (fa/fa).

Previously we found that adult Zucker fatty rats have C-cell hyperplasia and increased thyroidal calcitonin (CT) compared to lean controls. In this study we have evaluated both secretion of CT and responsiveness to CT in order to see whether they, too, were altered. Fat rats and lean littermates, 13-15 months old, were used. CT secretion was provoked by (1) feeding for 2 hr after an 18-hr fast, (2) giving pentagastrin iv, and (3) injecting CaCl2 iv. CT was measured by radioimmunoassay. Responsiveness to CT was examined by giving porcine or salmon CT iv and measuring serum Ca 1-3 hr later. For CT secretion, compared to leans the fat rats showed (1) higher fasting serum Ca and CT and a greater rise in CT after feeding, (2) a similar 5- to 10-fold increase in CT after iv pentagastrin, and (3) a greater rise in both serum Ca and CT at various times between 5 min and 3 hr after iv CaCl2. For CT responsiveness, fat and lean rats were equally responsive to iv CT in terms of the fall in plasma Ca 1-3 hr later. The results show that fat rats can secrete as much or more CT in response to provocative stimuli as lean rats and that they appear normally responsive to injected CT. Therefore, inability to release CT and insensitivity to CT do not underly the C-cell hyperplasia, increased thyroidal CT, and increased circulating CT in the fat rat.

Animals↗
PubMed1982

Thyroid venous catheterization in the early diagnosis of familial medullary thyroid carcinoma.

In kindreds with familial medullary thyroid carcinoma (MTC), individuals are often detected whose peripheral plasma calcitonin (CT) levels are undetectable in the basal state but increase minimally following provocative testing. The proper management of such patients has been uncertain, but most investigators have advocated repeat testing and evaluation after an interval of several months. The present study was conducted to evaluate the diagnostic implications of these modest increases in plasma calcitonin. In 25 kindred members at direct risk for familial medullary thyroid carcinoma (MTC), basal peripheral plasma calcitonin (CT) levels were less than 240 pg/ml. Following provocative testing with intravenous calcium or pentagastrin or both, calcitonin values remained below 240 pg/ml in eight subjects (Group A), however, they were mildly elevated (260-580 pg/ml) in 12 subjects (Group B) and moderately elevated (700-940 pg/ml) in five subjects (Group C). Following the transfemoral placement of a catheter into the inferior thyroid vein (ITV), provocative testing was repeated, and ITV and peripheral blood samples were collected simultaneously. Basal ITV plasma CT levels were below 240 pg/ml in all patients in Group A, however, they were mildly elevated (500 pg/ml) in one of the 12 patients in Group B and moderately elevated (800 pg/ml, 1400 pg/ml) in two of the five patients in Group C. Following provocation, ITV plasma CT levels became markedly elevated in one patient in Group A and in all of the patients in Groups B(2520+/-635 pg/ml) and C (6322+/-2598 pg/ml). Thyroidectomy was performed in patients whose ITV plasma CT level was elevated following provocative testing. Medullary thyroid carcinoma of C-cell hyperplasia were evident either on microscopic (1/1 patient in Group A;9/12 patients in Group B; and 2/5 patients in Group C), or gross (3/12 patients in Group B;3/5 patients in Group C) examination of thyroidectomy specimens. In only one of 14 patients was metastatic MTC noted on histologic examination of resected cervical lymph nodes. Postoperative peripheral plasma CT levels were unchanged from basal and less than 240 pg/ml following provocative testing in all but one patient. The present study then provides definitive evidence that patients at direct risk for familial MTC who have even minimally abnormal responses in peripheral plasma CT following provocative testing generally harbor some stage of a C-cell proliferative disorder. Identification of such individuals with early disease is important because thyroidectomy offers an extremely high cure rate.

Adolescent↗
PubMed1982

Magnesium promotes both parathyroid hormone secretion and adenosine 3',5'-monophosphate production in rat parathyroid tissues and reverses the inhibitory effects of calcium on adenylate cyclase.

Reduced extracellular Ca2+ is known to promote PTH secretion, while severe Mg2+ depletion has the opposite effect. We have correlated the effects of Mg2+ and Ca2+ on parathyroid hormone (PTH) secretion and cAMP accumulation by rat parathyroid tissues in vitro with the effects of these two metals on adenylate cyclase activity in broken membrane preparations. PTH secretion was maximal at 0.5 mM Ca2+, falling to low levels as the Ca2+ concentration was increased to 2.5 mM. Deletion of Mg2+ from the medium resulted in a marked decrease in PTH secretion at any given Ca2+ concentration. At a constant Ca2+ concentration of 1 mM, both PTH secretion and cAMP production rose to maximal rates as the Mg2+ concentration was increased from 0 to 2 mM. The adenylate cyclase of rat parathyroid membranes was stimulated by both GTP and guanyl-5'-yl-imidodiphosphate [Gpp(NH)p]. EDTA-treated membranes could not be stimulated by Gpp(NH)p. Repletion with Mg2+ was more effective than repletion with Ca2+ in restoring responsiveness to the guanine nucleotide. When membranes were maximally preactivated by Gpp(NH)p and then assayed in the presence of variable concentrations of metal ions, enzyme activity was directly inhibited by Ca2+ and stimulated by Mg2+. Adenylate cyclase sensitivity to Ca2+ inhibition was dependent upon the Mg2+ concentration; in the presence of 0.6 mM Mg2+ a 50% inhibition was produced by 0.05 mM Ca2+, while in the presence of 8 mM Mg2+ a 10-fold higher Ca2+ concentration was required for a similar inhibitory effect. The results suggest that Ca2+ may decrease PTH secretion at least in part by a direct inhibition of adenylate cyclase. Mg2+ may promote PTH secretion either by enhancing the activation of adenylate cyclase by endogenous guanine nucleotides or by competing with Ca2+ for binding to a distinct regulatory site on the enzyme.

Adenylyl Cyclase Inhibitors↗
PubMed1981

Presence of immunoreactive calcitonin in the hypothalamus and pituitary lobes of rats.

We have found calcitonin-like immunoreactive material in extracts of hypothalami from six-month old, male rats. The level of this immunoreactivity, 0.21 ng/hypothalamus, is substantial considering out lower limit of detection of 0.006 ng of rat calcitonin. However, the hypothalamus contains less calcitonin-like immunoreactive material than either the anterior lobe (1.16 ng) or neurointermediate lobe (0.81 ng) of the pituitary. Taken together these three sources of calcitonin-like immunoreactive material contain less than one thousandth the immunoreactivity found in the thyroid. The exact nature of the calcitonin-like immunoreactive material found in these extrathyroidal sites and its physiological role, if any, remain to be discovered. The recent report of the occurrence of calcitonin receptors in the hypothalamus and other brain regions in conjunction with our finding of calcitonin-like immunoreactivity in the hypothalamus suggests that calcitonin-like molecules may be active within the brain.

Animals↗
PubMed1981

Stimulation of in vitro release of calcitonin from rat and human C-cells by cimetidine.

Previous reports have suggested that the H2-receptor blocker, cimetidine, can inhibit parathyroid hormone (PTH) release. The present studies were designed in an attempt to see whether cimetidine affects secretion of calcitonin (CT) as well. Entire thyroparathyroid glands from 8-day-old baby rats or small pieces of a human medullary thyroid carcinoma were incubated at 37 C for up to 8 h in chemically defined culture medium gassed with 95% 02-5% CO2. With rat thyroparathyroids, both CT and PTH released into medium were measured using RIAs that detect that rat hormones. CT secreted from human C-cells was measured using an RIA for human CT. The results were: (A) As we had found previously, cimetidine at doses of 3 x 10(-3) M and 9 x 10(-3) M inhibited PTH release from rat thyroparathyroids by as much as 50-60% (p less than 0.05 - less than 0.001). In these same experiments, cimetidine produced increases of approximately 1- to 5-fold in the CT levels found in the medium (p less than 0.05 - less than 0.001). (B) Fragments of human medullary thyroid carcinoma incubated for 3 h in the presence of 10(-5) M cimetidine released considerably more CT than tissue incubated in control medium (48 +/- 9.3 vs 21 +/- 3.6 ng CT/microgram tissue protein, p less than 0.05). Our results show that cimetidine in vitro not only can inhibit secretion of PTH but also apparently can promote the release of CT from both rat and human C-cells. Whether this effect is mediated by H2 receptors and whether it is of any physiological significance awaits clarification.

Animals↗
PubMed1980

Calcitonin-like immunoreactivity in rat and human pituitary glands: histochemical, in vitro, and in vivo studies.

This study was designed to determine whether pituitary glands contain an immunoreactive material which reacts with antisera to calcitonin (CT) and, if so, whether secretion of the material could be demonstrated. Testing 15 antisera to rat and human CT and using an immunoperoxidase method, we found 2 antisera to human CT which stained rat pituitaries and several which stained human pituitaries. Essentially all cells in the rat intermediate lobe and scattered cells in the rat and human anterior lobes showed staining, and staining was not entirely abolished by prior adsorption of antisera with rat or human CT. The 2 antisera which stained rat pituitaries showed cross-reactivity with several synthetic human CT fragments (1-18, 11-23 and 22-32) but not with ACTH-(1-39), ACTH-(1-24), beta-endorphin, alpha- or beta MSH, or bovine lipotropin. Crude extracts of pituitaries from 2 strains of young rats showed CT-like immunoreactivity which could be measured easily by RIA (0.2-0.3 ng/gland). In vivo, an antiserum which stained pituitaries and 1 which did not were compared using young rats made hypercalcemic (15-20 mg/dl) with iv Ca. In rats with thyroids, both antisera showed an increase in serum CT of more than 15-fold whether the pituitary was present or absent. In thyroidectomized rats, serum CT remained undetectable (less than 50 to 100 pg/ml) during hypercalcemia even if the pituitary was present. In vitro, rat pituitaries in a serum-free medium did not release measurable amounts of immunoreactive CT-like material even when medium contained high Ca (2.5 mM), high K (25 mM), or TRH (10(-6) M). Therefore, the findings agree with other reports of a CT-like material in the pituitary, but no secretion of the material could be demonstrated. We hypothesize that the material is not authentic CT but is, rather a related peptide sequence probably contained in the 31 K precursor protein of ACTH-beta-lipotropin.

Amino Acid Sequence↗
PubMed1979

Effects of calcium and cyclic nucleotides on rat calcitonin and parathyroid hormone secretion.

Recently we developed a system for studying concurrent secretion of calcitonin (CT)and parathyroid hormone(PTH)in vitro from single rat thyroparathyroid gland complexes. In the present study, mechanisms involved in secretion of CT and PTH were explored by altering the medium [Ca ] and by using the Ca antagonist, verapamil. We also re-examined the idea that cyclic nucleotides may help regulate secretion of these hormones and attempted to determine if effects of cyclic nucleotides might be altered by changes in medium [Ca]. Thyroparathyroid glands from 8-day-old rats were incubated in serum-free medium for 8h, and CT and PTH levels in the medium were measured by radioimmunoassays. We show for the first time that: (1) although low [Ca] is well known to promote PTH release, some extracellular Ca is needed for PTH secretion to occur at a maximal rate; (2) inhibition of Ca entry into cells with verapamil mimics the effects of low medium Ca on both CT and PTH release; and (3) cyclic nucleotides may exert their effects on secretion of CT and PTH at least in part via effects on Ca entry into cells.

Animals↗
PubMed1978

Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland.

Twenty-six patients with known or suspected medullary thyroid carcinoma (MTC) and 21 normal control subjects were tested intravenously on four separate days with calcium gluconate (CG), 2 mg Ca(++)/kg/1 min.; pentagastrin (P), 0.5 ug/kg/ 5 sec.; calcium chloride (CC), 3 mg Ca(++)/kg/10 min.; and a combination of calcium gluconate and pentagastrin (CG + P). Calcitonin (CT) levels were determined by radioimmunoassay on plasma collected before and immediately following each test infusion. In none of the 21 control subjects was there a clear increase in CT above 200 pg/ml following any of the four provocative tests. Conversely, in all 26 patients with known or suspected MTC, plasma CT levels were markedly increased (>300 pg/ml) following the combined infusion of CG + P. The peak CT response was greater with CG + P than with a) CG alone (22 of 24 patients, p < 0.002), b) P alone (25 of 26 patients, p < 0.002), or c) CC alone (17 of 17 patients, p < 0.002). Of 12 MTC patients with undetectable basal calcitonin levels, all had peak responses greater than 300 pg/ml following CG + P, whereas such responses occurred less often following CG alone (8 of 12) or P alone (8 of 12). The results demonstrate that the combined administration of pentagastrin and calcium gluconate constitutes a more effective and reliable stimulus for CT secretion from MTC cells than the use of either agent alone, and appears the most useful single screening test for the detection of occult MTC.

Adolescent↗