Effect Of Porcine Calcitonin Research Articles

Intrathecal porcine calcitonin enhances the release of [Met 5]enkephalin-like material from the rat spinal cord

Perfusion of the intrathecal space of halothane-anaesthetized rats with artificial cerebro-spinal fluid supplemented with porcine calcitonin (1–10 μM) produced a significant increase (+67–110%) in the spinal release of [Met 5]enkephalin-like material. The effect of porcine calcitonin was markedly enhanced (+100%) in animals receiving a continuous i.v. infusion of the opioid antagonist naloxone (65 μg/kg per min). These data strongly suggest that the antinociceptive effect of intrathecal porcine calcitonin might involve a stimulatory action of the hormone on spinal enkephalinergic interneurones. In addition, presynaptic opioid autoreceptors probably control the activity of these neurones in the rat.

Effects of porcine calcitonin on behavioral and electrophysiological responses elicited by electrical stimulation of the tooth pulp in rabbits.

Effects of porcine calcitonin on both behavioral and electrophysiological responses of rabbits to painful stimuli were examined. The behavioral pain response (licking reaction) to electrical stimulation of the tooth pulp was suppressed dose dependently by intracerebroventricular administration of calcitonin, 8 and 17 U/kg, but not by intravenous injection of 7.5-50 U/kg of the peptide. The duration of action of intracerebroventricular calcitonin was over 90 min. The EEG arousal response and the development of the long latency cortical potential evoked by electrical stimulation of the tooth pulp in gallamine-immobilized rabbits, were inhibited by intracerebroventricular calcitonin, 17 U/kg, for the period of over 90 min but not by the intravenous injection of 50 U/kg. Morphine, 2 mg/kg i.v., inhibited all of the responses for 30 min or longer. The EEG arousal response induced by sound stimulation was not affected by calcitonin or morphine. Naloxone (0.5 mg/kg i.v.), an opiate antagonist, showed no influence upon the inhibitory effects of calcitonin in licking reaction, EEG arousal response and evoked potential, though it completely antagonized the effects of morphine. The results suggest that the analgesic effect of intracerebroventricular porcine calcitonin can be attributed to blocking of pain pathways in the central nervous system in a manner distinct from the narcotic analgesic.

The effect of porcine calcitonin on intestinal calcium and phosphate fluxes in the young piglet

The effects of a physiological (3.8 ng.mL-1) and a pharmacological (120 ng.mL-1) concentration of porcine calcitonin (CT) on transmucosal calcium and phosphate flux rates were determined in intestinal mucosa from young piglets (4--40 days) mounted in Ussing flux chambers. The physiological concentration of the hormone inhibited net absorptive calcium flux rates in the proximal jejunum and distal ileum but not in the duodenum. No effect of either concentration of CT on phosphate flux rates was observed. The inhibitory effect of the physiological concentration may indicate a role for CT in the maintenance of calcium homeostasis in the young suckling mammal.

Evoked potential studies of porcine calcitonin in rabbits

Effects of porcine calcitonin on evoked potentials of rabbits to painful stimuli were examined. The development of the long latency cortical potential evoked by electrical stimulation of both the tooth pulp and sciatic nerve in gallamine-immobilized rabbits was inhibited by i.c.v. calcitonin of 17 U/kg, but not by the intravenous injection of 50 U/kg. Pretreatment with naloxone (0.5 mg/kg i.v.) showed no influence upon the inhibitory effect of calcitonin, though it completely antagonized the effect of morphine. The results suggest the analgesic effect of i.c.v. porcine calcitonin can be attributed to blocking of pain pathways in the central nervous system in a manner distinct from the narcotic analgesic.

Effects of ketoprofen on the calciuric and uricosuric activities of calcitonin in man.

The action of ketoprofen on the calciuric and uricosuric effects of porcine calcitonin in man is reported. The drug is capable of inhibiting both effects. This action is considered like an effect on CT receptors in the kidney or a competitive action on prostaglandin synthesis.

The effect of porcine calcitonin on plasma calcium in Channa punctatm Bloch

The effect of porcine calcitonin on the plasma calcium of the freshwater Indian murrel, Channa punctatus Bloch has been studied. An injection of 200 MRC mU of porcine calcitonin was given intraperitoneally, while control fish received the gelatin carrier. A significant hypocalcaemia was noted I h after calcitonin treatment (P < 0.001). The plasma calcium had returned to the normal level by the 6th h.

Effects of various calcitonins on calcium concentrations in the bile and serum of thyroparathyroidectomized rats.

The effects of porcine calcitonin (CT), salmon CT, or synthetic eel CT ( [Asu1, 7] ECT) on the calcium concentrations in the bile and serum have been examined after a single intraperitoneal administration of calcium chloride to thyroparathyroidectomized rats. The administration of these hormones (80 MRC mU/100 g body weight, respectively) markedly increased calcium excretion into the bile within 1 hr after the injection of calcium chloride (4.0 mg Ca/100 g). The effect of synthetic eel CT was more prolonged than that of any other hormone (up to 3 hr after administration). The administration of porcine CT, salmon CT, or synthetic eel CT significantly inhibited the elevation of serum calcium concentration within 1 hr after the injection of calcium. The serum calcium concentration was slightly decreased at 3 hr after the administration of salmon CT or synthetic eel CT. These results suggest that the lowering effect of CT on the serum calcium level results partly from the stimulation of calcium excretion into the bile.

A quantitative study of the effects of prolonged calcitonin treatment on alveolar bone remodelling in the golden hamster.

This study was carried out on adult golden hamsters, to correlate the effects of porcine calcitonin on serum Ca and P concentrations with changes in osteoclastic resorption of bone. After 1 month of treatment with 5 MRC units/kg/day, there was little effect on these parameters. On the other hand, the hormone appears to have an effect on the remodelling sequence, as indicated by a large and very significant decrease in the extent of resorption lacunae unoccupied by osteoclasts. It is suggested that the duration of the reversal phase, separating the end of active resorption from the beginning of active bone formation in each remodelling focus, is greatly decreased. This shortening is associated with a prolongation of the bone formation phase, and the extent of osteoid tissue is markedly and proportionally increased in the treated animals. After a prolonged administration, calcitonin does not seem to impede the formation of new osteoclasts, their number being only slightly diminished, but it remains possible that it does continue to inactivate these cells. The effect on the bone remodelling sequence could be either due to direct action on the osteoblasts or their percursor cells, or an indirect action via the osteoclasts.

Clinical, Biochemical and Histological Observations on the Effect of Porcine Calcitonin in Paget's Disease of Bone*

The response to porcine calcitonin has been assessed in 38 patients with Paget's disease, observed during 44 treatment periods of from three to 42 months. In 36 of the treatment courses significant relief of pain was achieved but the contribution of placebo effect could not be determined. Serum alkaline phosphatase and urinary hydroxyproline levels reached normal in a few patients, but the grouped data indicated a plateau effect above the range of normal. The acute hypocalcaemic response to calcitonin was lost only in those patients whose bone turnover was restored to normal. Quantitative histology on iliac crest bone biopsy samples showed no statisically significant lowering of osteoclast counts. No antibody-based clinical resistance occurred and the incidence of side effects was low. The results indicate that porcine calcitonin is a useful treatment of Paget's disease, and the experience of the study helps in arriving at patient selection and treatment schedules. Treatment is recommended for bone pain and for active disease in the relatively young, using intermittent therapy with course of at least six months duration. Resumption of therapy is based on clinical and biochemical indications.

Acute Responsiveness to Calcitonin in Chronic Renal Failure

The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.

Effect of porcine calcitonin in primary hyperparathyroidism (author's transl)

In order to investigate the effect of calcitonin (CT) on calcium and phosphorus metabolism in primary hyperparathyroidism (PHP), porcine calcitonin (80 MRC units) was injected intramuscularly at 9:00 a.m. and 5:00 p.m. for 10-14 days in 7 patients with parathyroid adenoma. Fasting blood specimens were drawn at 8:00 a.m. every other day and 24 hour urine samples were collected through out control and test days. To examine the acute effect of CT, blood and urine were checked several times until 8 hours after the first injection. A fall in the fasting serum calcium level observed in 5 patients during the repeated administrations of CT, as well as that observed in 6 patients within 6 hours after the first injection, showed a significant correlation with the initial serum calcium level. Serum phosphorus concentration decreased in all patients 6 hours after the first injection, while fasting levels seemed to remain unchanged. During the repeated administrations, urinary excretion of calcium and phosphrus decreased correspondingly with the fall in serum calcium levels, although no definite tendancy was observed within 8 hours after the first injection. Fasting serum PTH levels during the repeated administrations were measured in 2 patients. In a patient whose serum calcium returned to the initial level on the 7th day of administration, a gradual rise of PTH was observed, while in another patient whose serum calcium was kept lower than the initial level, PTH remained almost unchanged. These results indicate that, under such a condition where there is marked increase of bone resorption as PHP, repeated administrations of CT bring about not only a hypocalcemic effect but also the reduction of calcium and phosphorus excretion through a decreased filtered load. In addition, it was suggested that, in some cases of PHP, the hypocalcemic effect of CT may be abolished by an increase of PTH secretion from the parathyroid glands during long-term administration.

The Effect of Porcine Calcitonin on Osteoporosis Induced by Adrenal Cortical Steroids

Effects of porcine calcitonin (five MRC units per kilogram per day) on development of osteoporosis induced by cortisone (fifteen milligrams per kilogram per day) have been investigated in adult rabbits. Measurements of surface undergoing resorption and formation were determined from cross sections of femoral mid-diaphyses, femoral metaphyses, ribs, and vertebral bodies using the quantitative microradiographic method of Jowsey. Intact femora and vertebral bodies were evaluated for gross rarefaction by high resolution macnoradiography. Bone mass per unit area was determined and mineral content of femora, ribs, and vertebrae was esimated by ashing. Cortisone treatment alone: (1) decreased bone formation and increased bone resorption at all skeletal sites evaluated, (2) decreased the amount of bone mass per unit area in both cortical and cancellous specimens, (3) caused gross macroradiographic rarefaction of femora and vertebral bodies, and (4) reduced the ash weight of ribs and vertebrae. Calcitonin treatment alone: (1) increased bone formation in cortical specimens and reduced bone resorption in vertebral bodies, (2) caused increased density of metaphyseal zones of vertebral bodies as shown by macroradiognaphy, and (3) increased the ash content of femora, ribs, and vertebrae. When compared with specimens removed from animals receiving only cortisone, specimens removed from animals receiving both hormones exhibited: (1) reduction in bone resorption rates in the cancellous specimens, (2) increased rates of bone formation in femoral diaphyses, (3) increased mass per unit area in both cortical and cancellous bone, (4) less macroradiographic rarefaction of femora and ventebral bodies, and (5) increased ash content of vertebral bodies. These results support the possibility that exogenous calcitonin may be capable of retarding some of the detrimental effects of the adrenal cortical steroids on osseous tissue, especially cancellous bone.

Effect of porcine calcitonin on bone resorption in adult rats and mice.

Porcine calcitonin was administered twice daily at rates of 50 or 5 MRC U/kg/day to 25-month-old mice which had been chronically labelled with <sup>45</sup>Ca. No consistent effect of the hormone on isotope excretion was observed over a 25-day period. Similar results were observed when calcitonin was administered to <sup>45</sup>Ca- labelled 10-month-old rats at rates of 100 or 10 U/kg/day. The higher level induced a depression in <sup>45</sup>Ca excretion for about 10 days but was ineffective thereafter. Both levels induced an increase in urine Ca excretion. These experiments indicate that porcine calcitonin is not effective in inhibiting bone resorption in adult rats or aged mice.