Date of Award

1982

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

Al Swonger

Abstract

Serum ionized calcium has Ions been viewed as the physiologically active form of calcium yet the paucity of studies concerned with this response measure is apparent and maw be related to the high cost of modern potentiometric instrumentation. Reducing the cost factor was approached by integrating an inexpensive static-type calcium ion-specific electrode into a fabricated plastic electrode chamber. Characterization of the electrode system was performed by elucidating the optimum parameters for electrode use in serum samples. Conformance to the extended Nicolsky-Eisenman equation was used as a criterion for acceptable electrode system Performance. Negligible effects of proteins on the performance of the electrode was established by comparing calcium binding kinetics and PH dependence data obtained with the system with values obtained from the literature. The electrode system was shown to correlate well when compared with the Orion SS-20 serum ionized calcium instrument with over 97% of the variance accounted for by regression. The administration of calcium chloride or the divalent cation chelatorr ethylene diamine tetraacetic acids to rats resulted in predictable responses in serum ionized calcium. The serum ionized calcium electrode system was employed in tests of hypotheses concerning serum ionized calcium and antidepressant activity of the tricyclic antidepressant, protriptyline and the thyroid hormone' tri-iodothyronine. Rats treated with protriptyline (10ms/ks> for 1, 6 or 18 days and tested 2, 6, 12 and 24 hours after the last dose failed to show significant changes in serum ionized calcium. Similarly, animals treated with tri- iodothyronine at varying doses for 1, 5 or 10 days and tested 1, 4 or 24 hours after the last dose also failed to show changes in this response measure. Concomitant thyroid hormone at varying doses and protriptyline (5ms/kg) did not result in changes in serum ionized calcium or in any response measures studied which are either known or are suspected to be reflective of changes in calcium homeostasis. The results failed to support a calcium hypothesis of antidepressant activity. The results are at variance with those of clinical studies among depressives reported in the literature. Discussion offers support for viewing the rat as a Poor animal model for studying alterations in calcium homeostasis.

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