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C W Cooper

Publications and source records attributed to C W Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effect of gastrin-releasing peptide analogues on gastrin and somatostatin release from isolated rat stomach.

A differential biological potency of bombesin (BBS), compared with its mammalian counterpart gastrin-releasing peptide (GRP), has been reported in several biological systems in rodents. In the present study we have examined the relative potency of BBS, GRP-(1-27) (GRP-L), and GRP-(14-27) (GRP-S) on the release of gastrin and somatostatin (SRIF) from the isolated perfused rat stomachs. Male rats were fasted overnight and the stomachs perfused via the celiac artery. Increasing doses of BBS, GRP-L, and GRP-S were perfused for 15 min each and the effluent collected for measurement of gastrin and SRIF. The release of gastrin and SRIF in response to the GRP analogues was biphasic, with a peak increase occurring within the first 5 min, followed by a sustained increased secretion. The release of gastrin in response to 10(-10)-10(-9) M concentrations of the peptides was strongest with GRP-S (1.5-2.0 times higher than that released by BBS and GRP-L), although at higher concentrations (10(-8) M), the response to all three analogues was similar. The release of SRIF, on the other hand, was significantly higher in the presence of BBS compared with that in response to GRP-S, while GRP-L was ineffective. These studies indicate that the biological potency of BBS compared with its mammalian counterpart, GRP, is different on the two cell populations [gastrin (G) and SRIF (D)].

Animals↗
PubMed1987

Calcitonin, calcitonin gene-related peptide and renal calcitonin receptors in the Zucker rat.

In this study we investigated (a) whether genetically obese Zucker rats exhibit higher levels of calcitonin gene-related peptide (CGRP) in the thyroid and plasma than lean controls, (b) if CGRP, like calcitonin (CT), increases in plasma in response to iv Ca or iv pentagastrin and (c) whether or not renal CT receptors exhibit 'downregulation' in fat rats compared to leans. Fat and lean rats 8-12 months old were used. Compared to leans, fat rats exhibited higher circulating levels of CGRP as well as CT. Also, the total thyroid content (micrograms per gland) and concentration (ng/mg wet weight) of CGRP were higher in fat rats. One minute after iv pentagastrin, both lean and fat rats showed a marked increase in plasma CT but not plasma CGRP. In another experiment involving only lean rats, iv Ca given 4 min earlier produced a massive increase in plasma CT but no detectable increase in plasma CGRP. Using renal membranes and 125I-sCT as the ligand, we found that renal CT receptors in fat rats appeared more abundant than in lean rats and exhibited the same KD (3-6 nM) for both. The findings show that, compared to leans, fat rats have higher levels of CGRP as well as CT in the thyroid gland and blood. However, stimulation of C-cell release of CT was not accompanied by a corresponding rise in plasma CGRP, suggesting that either (a) the plasma CGRP is derived largely from non-thyroidal sources and the adult rat thyroid releases only trivial amounts of CGRP or (b) Ca and pentagastrin are secretagogues for thyroidal CT but not CGRP. Examination of renal CT receptors in fat and lean rats provided no evidence for downregulation of receptors in fat rats exposed chronically to higher circulating levels of CT than leans.

Animals↗
PubMed1987

Calcitonin gene-related peptide: possible tumor marker for medullary thyroid cancer.

We have sought to determine whether medullary thyroid carcinoma (MTC) released calcitonin gene-related peptide (CGRP) in vivo. MTC cells were inoculated from tissue culture into eight Wag-Rij rats. One month later blood was drawn before and after the intravenous injection of calcium, and plasma levels of CGRP and calcitonin (CT) levels in that blood were determined by radioimmunoassay. The tumor was examined for content of CGRP and of CT by means of radioimmunoassay and immunocytochemistry. The tumor was divided and portions were passed to another eight rats. One month later, the studies were repeated. The tumor was passed two additional times (four passages in all). Controls consisted of non-tumor-bearing Wag-Rij rats. Basal levels of plasma CGRP in control rats (7 +/- 1 ng/ml) were unaffected by calcium stimulation. In tumor-bearing rats, the plasma CGRP level, which was initially slightly elevated (15 +/- 7 ng/ml), rose progressively with passages to 279 +/- 79 ng/ml in the third passage and fell to normal values at the end of passage four. Hypercalcemia had no effect on plasma CGRP levels in tumor-bearing rats but did stimulate the release of CT in both control and tumor-bearing rats, although it is not clear whether this release was from the tumor or from normal thyroid parafollicular cells in these tumor-bearing rats. We conclude that rat MTC synthesizes and releases CGRP but, unlike CT, CGRP appears unresponsive to calcium stimulation.

Animals↗
PubMed1986

Calcitonin and calcitonin gene-related peptide enhance calcium-dependent potentials.

Recent data suggests that calcitonin (CT) and/or calcitonin gene-related peptide (CGRP) may be potential transmitters or modulators in the nervous system. The present study analyzed the effect of CT and CGRP on the neuronal membranes of cat parasympathetic ganglia of the urinary bladder. The related peptides prolonged the duration of the afterhyperpolarization of the action potential but had no effect on resting potential or input resistance. CT and CGRP enhanced the duration of a calcium spike recorded in the presence of agents blocking Na and K channels while under similar conditions forskolin, an activator of adenylate cyclase, did not affect the calcium spike. These data suggest that the neural mechanism of action of CT and CGRP is to prolong a calcium conductance and that these effects are not mediated through cyclic AMP.

Action Potentials↗
PubMed1986

Motor effects of calcitonin administered intracerebroventricularly in the rat.

In rats treated with salmon calcitonin (CT) administered intracerebroventricularly (i.c.v., 85 or 8.5 pmol), spasmodic body movements, hopping and tail jerks, collectively termed dyskinesia, appeared within 1 h of administration and persisted for at least 24 h. In addition, spontaneous grooming, rearing and locomotion occurred less often in CT-treated rats than in vehicle-injected animals, while the incidence of both sniffing and nose poking remained essentially unchanged. The CT failed to displace either [3H]dopamine or [3H]spiperone from striatal membranes, and the behavioral effects were not blocked by haloperidol or SCH 23390, suggesting that the peptide did not directly affect dopamine receptors. The dyskinesia was not blocked by scopolamine, atropine, muscimol, diazepam or ketanserin. These data are consistent with the hypothesis that a compound with recognition characteristics similar to those of salmon CT may function as a neurotransmitter-modulator in the central nervous system.

Animals↗
PubMed1986

Binding of calcitonin and calcitonin gene-related peptide to calvarial cells and renal cortical membranes.

Binding of calcitonin (CT) and calcitonin gene-related peptide (CGRP) to rat hemicalvariae and renal membranes was examined in an effort to determine whether CT and CGRP interact with the same bone cell binding site, and to see whether the binding pattern was similar for bone and renal cortex. Specific binding of 125I-salmon CT to rat calvariae was inhibited by unlabeled salmon, porcine, or human CT, but not by rat CGRP. Binding of 125I-rat CGRP to calvariae was inhibited by CGRP and high doses of salmon CT, but not by human or porcine CT. Binding of 125I-salmon CT to renal membranes was inhibited by unlabeled salmon CT or rat CGRP, but no specific binding of 125I-rat CGRP could be detected. The results suggest that separate bone cell receptors for CT and CGRP exist and that CGRP can interact with renal receptors for CT.

Animals↗
PubMed1986

Inhibition of secretion of rat calcitonin by calmodulin inhibitors.

Studies were designed to investigate the potential importance of calmodulin in release of calcitonin (CT) in response to an increase in the concentration of extracellular Ca. In vitro release of CT from baby rat thyroparathyroids incubated up to 8 h was examined at normal (1 mM) and high (2.5 mM) Ca in serum-free medium in the presence and absence of the potent calmodulin inhibitors, trifluoperazine (TFP) and N-(6-aminohexyl)-5-Cl-1-naphthalene sulfonamide (W-7). The drugs chlorpromazine (CLP) and haloperidol (HAL) which, like TFP, are anti-psychotic agents also were tested. In some studies release of parathyroid hormone (PTH) into medium also was studied. At 2.5 mM Ca, CT release was increased five- tenfold compared with 1 mM Ca while PTH was suppressed by approximately 80%. The increased release of CT induced by 2.5 mM Ca was inhibited 60-90% by 10(-4) M TFP and 10(-4) M W-7, but was unaffected by 10(-4) M CLP or HAL. In the presence of 1 mM Ca, the increased release of PTH also was inhibited significantly by 10(-4) M TFP and 10(-4) M W-7. In related in vivo studies, administration of TFP i.v. to rats just before induction of hypercalcemia with i.v. CaCl2 suppressed the increase in plasma CT normally observed 3 min later in a dose-related manner. The results show that calmodulin inhibitors can inhibit in vitro secretion of CT, and release of PTH as well. Additionally, inhibition of the in vivo CT response to a Ca challenge was observed within minutes of drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Antagonistic behavioral effects of calcitonin and amphetamine in the rat.

Using an automated testing apparatus, the hypermotility induced by amphetamine had previously been found to be inhibited by intracerebroventricular (ICV) administration of salmon calcitonin (CT). The present study used a computer-supported direct observational method to characterize further the interactions of CT and amphetamine. After treatment with amphetamine (1.5 mg/kg, IP), the incidence of rearing, nose poking, and locomotion was reduced in rats that were pretreated with 85 pmol salmon CT ICV; the incidence of sniffing and grooming remained unchanged. CT-induced dyskinesia, a unique consequence of central CT treatment, was attenuated but not abolished by administration of amphetamine. These results support the premise that a compound with receptor recognition characteristics similar to those of salmon CT may act as a neurotransmitter-modulator in the central nervous system.

Amphetamine↗
PubMed1986

Cyclic AMP and the vascular action of parathyroid hormone.

The involvement of tissue cAMP in the vasodilating action of parathyroid hormone (PTH) was investigated. The bovine active fragment bPTH-(1-34) was used in all studies. In anesthetized dogs, theophylline, a phosphodiesterase inhibitor, potentiated the hypotensive action of bPTH-(1-34) at the dose of 1 microgram/kg. The potentiation was related to the dose of theophylline infused. In an in vitro rat tail artery helical strip assay, dibutyryl cAMP produced dose-related relaxation in arginine vasopressin (AVP) constricted blood vessels. bPTH-(1-34) also produced dose-related relaxation in the tail artery constricted by AVP. In the presence of isobutylmethylxanthine, another phosphodiesterase inhibitor, the bPTH-(1-34) dose--response curve was shifted to the left, indicating potentiation. Imidazole, which has phosphodiesterase stimulating activity, significantly decreased the in vitro vasorelaxing effect of bPTH-(1-34). In addition, bPTH-(1-34) increased significantly the rat tail artery cAMP content. b-PTH-(1-34) oxidized with hydrogen peroxide lost its vasorelaxing activity and was also ineffective in increasing the tail artery cAMP content. All these data strongly suggest that cAMP may be involved in eliciting the vasorelaxing action of bPTH-(1-34).

1-Methyl-3-isobutylxanthine↗
PubMed1986

Effects of the calcium channel activator BAY-K-8644 on in vitro secretion of calcitonin and parathyroid hormone.

The recently discovered calcium (Ca) channel activator BAY-K-8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate], an analog of the calcium channel blockers nifedipine and nitrendipine, was tested to determine its potential for altering hormone secretion in an in vitro system designed to study concurrent secretion of calcitonin (CT) and PTH. Addition of BAY-K-8644 (10(-4)-10(-5) M) to medium (1 mM Ca) bathing baby rat thyroparathyroids enhanced secretion of CT at least 2- to 4-fold and suppressed PTH release by as much as 75-85%. Addition of BAY-K-8644 alone to medium containing high (2.5 mM) Ca did not further enhance the already high rate of CT release, nor did it cause any further suppression of PTH secretion. BAY-K-8644 did not stimulate CT release or suppress PTH release in the absence of medium Ca. Addition of the Ca channel blocker nitrendipine (10(-5) M) inhibited CT release at either 1 or 2.5 mM Ca, and at 1 mM Ca, nitrendipine negated the simulatory effect of 10(-5) M BAY-K-8644 on CT release. However, at 2.5 mM Ca, 10(-5) M BAY-K-8644 reversed the marked inhibitory effect of 10(-5) M nitrendipine on CT release. At 1 mM Ca, PTH secretion was inhibited equally well by BAY-K-8644 and nitrendipine, and both agents together caused a further suppression of PTH release. The results indicate that Ca entry into the thyroid C-cell and parathyroid chief cell may occur via classical voltage-sensitive Ca channels and that the newly described Ca channel activator BAY-K-8644 should prove useful as a probe for studying hormone secretion in Ca-dependent secretory systems.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Calcitonin inhibition of insulin release from isolated rat pancreatic islets.

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.

Animals↗
PubMed1986

Antinociceptive activity of salmon calcitonin injected intraventricularly in mice: modulation of morphine antinociception.

Salmon calcitonin (sCT) was tested i.v.t. for its ability to produce antinociception in mice as quantitated by the tail-flick, hot-plate and p-phenylquinone (PPQ) writhing tests. sCT from two sources, Bachem (Torrance, CA) and Armour Pharmaceutical Co. (Chicago, IL), was shown to have naloxone reversible antinociceptive activity in the tail-flick and hot-plate tests. However, the sCT analgesic activity in the PPQ test was only partially naloxone reversible. sCT produced a naloxone reversible potentiation of doses of morphine that had low analgesic activity, but sCT failed to potentiate higher doses of morphine in the tail-flick test. sCT has a similar biphasic effect on morphine in the PPQ test in that low doses of morphine were selectively potentiated. However, the potentiation in the PPQ test was not naloxone reversible. sCT was shown not to be cross-tolerant to morphine in the PPQ test. Thus, sCT appears to produce its antinociceptive effects via interaction with both opiate and nonopiate mechanisms.

Analgesics↗
PubMed1985

Parathyroid hormone secretion from dispersed human hyperparathyroid cells: increased secretion in cells from hyperplastic glands versus adenomas.

The in vitro secretion of PTH by dispersed human parathyroid cells was examined under conditions of low and high extracellular Ca+2 using tissue from patients with primary hyperparathyroidism and hyperparathyroidism resulting from chronic renal failure (CRF). The PTH secretion rate (nanograms of PTH per 10(5) cells/h) was lower in adenomatous tissues than in either primary hyperplastic cells or CRF cells under conditions of low (0.5 mM) or high (2.0-3.0 mM) extracellular Ca+2. Among the adenomas, a wide spectrum of degree of suppressibility of PTH secretion by high Ca+2 was found, ranging from 0% (completely nonsuppressible) to 98%. Suppression of the hyperplastic tissues in general was similar. The most suppressible adenomas demonstrated 2-fold greater PTH secretion rates in low Ca+2 conditions than the least suppressible adenomas, but in high Ca+2 conditions, the two groups had similar secretory rates. We conclude that the rate of PTH secretion by cells from adenomas was substantially lower than that of cells from tissues exhibiting either primary hyperplasia or hyperplasia resulting from CRF under these in vitro conditions. Thus, in adenomas, an increase in absolute cell number as well as alterations in the degree of calcium responsiveness may prove to be important etiological factors in the expression of hyperparathyroidism.

Adenoma↗
PubMed1985

Secretion of calcitonin gene-related peptide from baby rat thyroid glands in vitro.

Thyroid glands from 8-day-old rat pups were incubated in serum-free medium for 6 hr. Both calcitonin (CT) and calcitonin gene-related peptide (CGRP) released into medium were measured by radioimmunoassay. In 6 separate experiments CGRP was easily detected in medium in ng/ml concentrations. In 4 of the 6 experiments, where CT release was stimulated by high medium [Ca], the concentration of CGRP in medium showed a positive, significant correlation with the medium CT concentration (r = 0.41-0.69, p less than .05- less than .01). The results are in concert with reports describing the presence of CGRP in the C-cell, and they further show that CGRP, as well as CT, can be secreted by C-cell.

Animals↗
PubMed1984

Divergent effects of forskolin on 3',5' cyclic adenosine monophosphate production and parathyroid hormone secretion.

Forskolin, a diterpene which directly stimulates adenylate cyclase, markedly stimulated cAMP production in intact rat parathyroid glands and dispersed cells from hyperplastic and adenomatous human parathyroid tissues. Stimulation of cAMP production in human parathyroid adenomas occurred as early as 2 min and continued for at least 2 h; furthermore, a dose-response relationship was observed, with a maximal 80-fold cAMP response occurring at 100 microM forskolin. When PTH secretion by rat or human parathyroid tissues was studied at low (0.5 mM) and high (2.5 mM) extracellular Ca2+ in either the presence or absence of forskolin, no significant stimulation by forskolin was observed at 15 min, 1 h, and 2 h. When 10 human parathyroid specimens were studied with varying concentrations of forskolin at 1 mM Ca2+, 6 failed to show stimulation of PTH secretion and 4 showed modest but detectable increases in PTH that did not appear dose-related. We conclude that (1) at low and high Ca2+ levels, marked stimulation of cAMP production by forskolin can occur without a corresponding increase in PTH secretion; (2) inhibition of PTH secretion by high extracellular Ca2+ levels continues unchanged despite stimulation of cAMP production by forskolin; and (3) at intermediate Ca2+ levels (1.0 mM), PTH secretion is affected either minimally or not at all by forskolin in human hyperparathyroid tissue preparations. The marked stimulation of parathyroid adenylate cyclase by forskolin without concomitant increases in PTH secretion in the majority of tissues suggests that the level of cAMP production is not a primary or sufficient determinant of hormone secretion.

Adenoma↗
PubMed1984

Effects of vitamin D and parathyroid hormone on cyclic AMP production by bone cells isolated from rat calvariae.

Studies presented here were designed to investigate further the basis for an impaired cAMP response to parathyroid hormone (PTH) in osteoblastlike calvarial bone cells isolated from vitamin D-deficient rat pups. The goal was to perturb Ca, PTH, and vitamin D in vivo in order to see which factors might be responsible for the impaired in vitro bone cell cAMP response. Pups either were parathyroidectomized (PTX) 3-5 days, implanted with osmotic minipumps delivering high doses of PTH, given repeated, high doses of 1,25(OH)2D3, or were D-deficient (-D, i.e., born and suckled by D-deficient mothers). Osteoblastlike bone cells, isolated by sequential enzyme digestion and centrifugation, were exposed to PTH for 5 min in the presence of a phosphodiesterase inhibitor. In bone cells isolated from -D rat pups, both basal and PTH-induced cAMP accumulation were significantly lower than in +D bone cells. Earlier, we had shown that two daily injections of -D pups with 50 ng 1,25(OH)2D3 restores this reduced bone cAMP response of -D pups toward normal. In the present study, neither basal nor PTH-induced bone cell cAMP accumulation was affected by subjecting D-replete pups to PTX, PTH infusion, or repeated high doses of 1,25(OH)2D3 despite the fact that each treatment markedly changed serum Ca or serum immunoreactive PTH. The results indicate that the impaired bone cell cAMP response seen in -D pups is not a direct result of chronic hypocalcemia and that the "heterologous desensitization" seen in vitro with added 1,25(OH)2D3 could not be duplicated by in vivo treatment of +D pups with supraphysiologic doses of 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Serum calcitonin, calcium and thyroxine in young and old Zucker fatty rats (fa/fa).

We determined the serum levels of calcitonin (CT), calcium (Ca), and thyroxine (Ti) in lean (?/+) and fatty (fa/fa) male Zucker rats 10 weeks and 10-12 months of age. The most dramatic finding was a high level of serum CT (3.24 +/- 1.18 ng/ml) in young fatties whereas sera from young leans were all below the limit of assay detection (less than 0.120 ng/ml, p less than 0.01). Young fat rats also had elevated levels of both Ca (11.2 +/- 0.2 vs. 9.7 +/- 0.2 mg/dl, p less than 0.001) and Ti (6.7 +/- 0.48 vs. 4.72 +/- 0.28 micrograms/dl, p less than 0.01). In older animals the mean serum level of CT increased further in the fatties and became readily measurable in leans (5.67 +/- 1.94 vs. 1.49 +/- 0.55, p less than 0.01). Thyroid C-cells, identified immunohistochemically, were abundant in both leans and fatties at this age but were substantially more numerous in the fat rats (p less than 0.001). Calcium levels increased somewhat in the older leans, but still remained higher in the fat rats (p less than 0.05). Thyroxine values were essentially the same for old animals of both genotypes (5.07 +/- 0.61 vs. 5.54 +/- 0.88). Age effects were not significant for any measure in the fat animals, but in the leans there were significant age-related increases in CT (p less than 0.02) and serum Ca (p less than 0.05).

Age Factors↗