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The hypocalcemic effect of calcium
LIFE SCIENCES Vol . 6, pp . 2009-2012, 1967 . Printed in Great Britain.
Pergamon Press Ltd.
THE HTPOCALCEMIC EFFECT OF CALCIUM George H. Theil and Jay R. Miller Departsmt of Mediciae, Oollege of Mediciae Uaivreity of Ioxa, Iara City, I~wa (Received 20 April 1967 ; in final form 14 July 1967) The existeaw of a plasma-calciua-lowering factor has been established (1,2).
Thin hypocalasdc principle xaa deeoostrated initially (1) by perfus-
ing isolated thyroidrparathyroid tissue, xhich rssaiaed in the circulation, xith solutims containing high concentrations of calcius (approxisiately 12 ~./100 sil) and then assa
A significmit fall in the plasma calcium level in the
bioassay animal (young sdnlt dog on lox calcium diet) following the injectim of plassia prepared fros this venous blood xas tM criteriao for a positiv hormonal effect .
Parallel experirats xere sisultaneously accomplished to
rule out the effect of parathoroaae suppression as the regulating mechanise. Other invstigators hav suggested that the hypophasphateatc response elicited in sooe species used for bioassay was less consistent thao the hypocalwnic effect (3) .
In neural experiments measuring thyrocalcitonin or oalcitcain
an attempt was made to prevent the return of the calcium of the perfusion solution to the systemic circulation by the use of ohelatiag agents or coluna chromatography (1,4) is order to circumvent say potential inllueace the calcium ion per se eight product.
Mo e~erimental information is available,
haeevr, regarding the effect that calcium alone might hav in the animal most commmly employed (rat) in the bioassay of thyrocalcitonin . Mathada Mali albino Holtzmsn .rats, weighing approxisately 160 P, xere injected iatraperitaneally with either 1 ml of physiological saline (0 .85
sodium
chloride) or 1 ml of physiological saline costuming 10 .0 mg of calcium per 2009
2010
HYPOCALCEMIC EFFECT
Yol . 6, No . 18
100 ml of saline (in the form of calcium chloride) . 10 rats in each group .
There were a total of
After 60 minutes the rata were sacrificed under ether
anesthesia by opening the abdominal cavity and collecting blood directly iron the abdominal aorta.
Calcium was smeared bq Cnlcein-EDTA titratica technique
(5) and inorganic phosphatas by the Fiske and Subbarow method (6) .
Haaal
control values xera obtained during each experimental rim bq similarly collecting aortic blood from a separate group (group I) of 10 control animals .
The
blood specimens in each instance were collected in hapariniaed tubes and imasdiately spun dam to seps~ata the plasma .
All rats were fed standard lab-
oratarq rat char . Results Table I indicates the effect that 1 ml of physiological saline and 1 nl of physiological saline containing 10 .0 mg of calcium per 100 cc of saline had an the plasma calcium and phosphorus lswls of the male albino Holtamea rate .
These results are shown in Group II and Group III of Table I and are
sompared to the basal concentrations ordinarilq found in the simultaneouslq studied control rata (Group I) .
There were no significant differences be-
tween the usual basal values of either calcium or phosphorera and the plasma concentrations sae hair following the iatraperitonsal administration of phgsiological saline (Group I versus Group II) .
On the other hand, the saline solu-
tiao containing the calcium produced a statistically significant (p<0 .05) lowering of both the plasma calcium and phosphorus levels in the experimental animal (Group I wrsue Group III) ; thus demaastrating that solutions with physiological eoocentratiooa of this ioniaable Lalt of calcium are capable of inducing an hypophoephatemic as well as an hgpocalcsmic reapmae. TAHLE I. The effect of the intraperitaraal injection of 1 ml of physiological saline are compared with the effects of 1 ml physiological saline containing 10 mg$ elemental calcium. The
HYPOCALCEMIC EFFECT
Yol . 6, No . 18
2011
results which these solutions had cn the planma calcium and phosphorus coacantraticn of the test animals are compared to the valace obtained in the basal atata ia a comparable group of control rats . (~ou~ III Hasel Control
Physiological Saline Control
Physiological Saline Containing 10 mg$ Elemental Calcium
Calcium m~$
10 .15 t 0 .13#
10 .00 ± 0.15
t9.33 ~ 0 .10
Phosphozvs mg$
10 .15 ± 0 .30
10 .25 ± 0.25
+9.17 ± 0.22
e
Standard error of the mean .
t
Group III values are significantly different from Group I sad II (p<0 .05)
by the method of multiple comparisons .
The data for calcium and phosphorus
are treated independently and each is eigaificant (values in Group I varaua Group III as wall as Group II varsua Group III) at the p<0 .05 level . Discussion These results suggest that calcium can bring about a calcium lowering affect in this experimental animal .
Whether this is horeionally mediated as
the raault of endogenous thtrocalcitanin stimulation to the assay animal is not )mown, and oannot be deduced fran these experiments .
However, if can
does attempt to assay thyroaalcitonin by employing the rat as the test animal it should be appreciated that calcium per ss is capable of inducing a response similar to that described for thyrocalcitcnin .
In terms of the
potential increase which intraperitoneal calcium might have cn the estimated body extracellular calcium of the rat, the challenge of the administered calcium is potentially very small (approximately 3$) ; assuming that all of the administered calcium in the saline-calcium solution wan absorbed from the peritanaal cavity .
Thin observation is made only to emphasize the apparent sen-
sitivity of this assay animal to relatively small amounts of calcium.
2012
HYPOCALCEMIC EFFECT
Vol . 6, No . 18
R~f~rsnas 1.
D .H, Copp, E .C . Cameron, B .A, Chewy, A .G.F . Davidson and K .G, Heaaa, Endrocriaolo~r 1 698 (1962) .
2.
P .F, Hirsch, E .F . Voalk~l, and P .L . Mimaoa, Scisna 146, 412 (1964),
3,
G .V, Fostar, A . Baghdiaata, !l,A . Kumsr, E . Slack, H,A . Soliman and I . MacIntyra, Natura 202, 1305 (1964) .
4,
A .D, Cara, Natura 205, 1289 (1965) .
5,
H . Diahl and J,L . EllinBba , Anal . Chain . 28, 822 (1956),
ö,
C .H, Fiska and Y . Subbarox, J . Hiol . Cham, 66, 375 (1925) .
Pergamon Press Ltd.
THE HTPOCALCEMIC EFFECT OF CALCIUM George H. Theil and Jay R. Miller Departsmt of Mediciae, Oollege of Mediciae Uaivreity of Ioxa, Iara City, I~wa (Received 20 April 1967 ; in final form 14 July 1967) The existeaw of a plasma-calciua-lowering factor has been established (1,2).
Thin hypocalasdc principle xaa deeoostrated initially (1) by perfus-
ing isolated thyroidrparathyroid tissue, xhich rssaiaed in the circulation, xith solutims containing high concentrations of calcius (approxisiately 12 ~./100 sil) and then assa
A significmit fall in the plasma calcium level in the
bioassay animal (young sdnlt dog on lox calcium diet) following the injectim of plassia prepared fros this venous blood xas tM criteriao for a positiv hormonal effect .
Parallel experirats xere sisultaneously accomplished to
rule out the effect of parathoroaae suppression as the regulating mechanise. Other invstigators hav suggested that the hypophasphateatc response elicited in sooe species used for bioassay was less consistent thao the hypocalwnic effect (3) .
In neural experiments measuring thyrocalcitonin or oalcitcain
an attempt was made to prevent the return of the calcium of the perfusion solution to the systemic circulation by the use of ohelatiag agents or coluna chromatography (1,4) is order to circumvent say potential inllueace the calcium ion per se eight product.
Mo e~erimental information is available,
haeevr, regarding the effect that calcium alone might hav in the animal most commmly employed (rat) in the bioassay of thyrocalcitonin . Mathada Mali albino Holtzmsn .rats, weighing approxisately 160 P, xere injected iatraperitaneally with either 1 ml of physiological saline (0 .85
sodium
chloride) or 1 ml of physiological saline costuming 10 .0 mg of calcium per 2009
2010
HYPOCALCEMIC EFFECT
Yol . 6, No . 18
100 ml of saline (in the form of calcium chloride) . 10 rats in each group .
There were a total of
After 60 minutes the rata were sacrificed under ether
anesthesia by opening the abdominal cavity and collecting blood directly iron the abdominal aorta.
Calcium was smeared bq Cnlcein-EDTA titratica technique
(5) and inorganic phosphatas by the Fiske and Subbarow method (6) .
Haaal
control values xera obtained during each experimental rim bq similarly collecting aortic blood from a separate group (group I) of 10 control animals .
The
blood specimens in each instance were collected in hapariniaed tubes and imasdiately spun dam to seps~ata the plasma .
All rats were fed standard lab-
oratarq rat char . Results Table I indicates the effect that 1 ml of physiological saline and 1 nl of physiological saline containing 10 .0 mg of calcium per 100 cc of saline had an the plasma calcium and phosphorus lswls of the male albino Holtamea rate .
These results are shown in Group II and Group III of Table I and are
sompared to the basal concentrations ordinarilq found in the simultaneouslq studied control rata (Group I) .
There were no significant differences be-
tween the usual basal values of either calcium or phosphorera and the plasma concentrations sae hair following the iatraperitonsal administration of phgsiological saline (Group I versus Group II) .
On the other hand, the saline solu-
tiao containing the calcium produced a statistically significant (p<0 .05) lowering of both the plasma calcium and phosphorus levels in the experimental animal (Group I wrsue Group III) ; thus demaastrating that solutions with physiological eoocentratiooa of this ioniaable Lalt of calcium are capable of inducing an hypophoephatemic as well as an hgpocalcsmic reapmae. TAHLE I. The effect of the intraperitaraal injection of 1 ml of physiological saline are compared with the effects of 1 ml physiological saline containing 10 mg$ elemental calcium. The
HYPOCALCEMIC EFFECT
Yol . 6, No . 18
2011
results which these solutions had cn the planma calcium and phosphorus coacantraticn of the test animals are compared to the valace obtained in the basal atata ia a comparable group of control rats . (~ou~ III Hasel Control
Physiological Saline Control
Physiological Saline Containing 10 mg$ Elemental Calcium
Calcium m~$
10 .15 t 0 .13#
10 .00 ± 0.15
t9.33 ~ 0 .10
Phosphozvs mg$
10 .15 ± 0 .30
10 .25 ± 0.25
+9.17 ± 0.22
e
Standard error of the mean .
t
Group III values are significantly different from Group I sad II (p<0 .05)
by the method of multiple comparisons .
The data for calcium and phosphorus
are treated independently and each is eigaificant (values in Group I varaua Group III as wall as Group II varsua Group III) at the p<0 .05 level . Discussion These results suggest that calcium can bring about a calcium lowering affect in this experimental animal .
Whether this is horeionally mediated as
the raault of endogenous thtrocalcitanin stimulation to the assay animal is not )mown, and oannot be deduced fran these experiments .
However, if can
does attempt to assay thyroaalcitonin by employing the rat as the test animal it should be appreciated that calcium per ss is capable of inducing a response similar to that described for thyrocalcitcnin .
In terms of the
potential increase which intraperitoneal calcium might have cn the estimated body extracellular calcium of the rat, the challenge of the administered calcium is potentially very small (approximately 3$) ; assuming that all of the administered calcium in the saline-calcium solution wan absorbed from the peritanaal cavity .
Thin observation is made only to emphasize the apparent sen-
sitivity of this assay animal to relatively small amounts of calcium.
2012
HYPOCALCEMIC EFFECT
Vol . 6, No . 18
R~f~rsnas 1.
D .H, Copp, E .C . Cameron, B .A, Chewy, A .G.F . Davidson and K .G, Heaaa, Endrocriaolo~r 1 698 (1962) .
2.
P .F, Hirsch, E .F . Voalk~l, and P .L . Mimaoa, Scisna 146, 412 (1964),
3,
G .V, Fostar, A . Baghdiaata, !l,A . Kumsr, E . Slack, H,A . Soliman and I . MacIntyra, Natura 202, 1305 (1964) .
4,
A .D, Cara, Natura 205, 1289 (1965) .
5,
H . Diahl and J,L . EllinBba , Anal . Chain . 28, 822 (1956),
ö,
C .H, Fiska and Y . Subbarox, J . Hiol . Cham, 66, 375 (1925) .