In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.kg-1 and 0.75 IU kg-1 IM, and 1.5 IU.kg-1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and pO2 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.
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Biochim Biophys Acta Mol Cell Res
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Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address:
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Division of Molecular Medicine, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
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Department of Pharmaceutics, School of Pharmacy, University of Washington.
The active metabolite of vitamin A, all-trans-retinoic acid (atRA), is critical for maintenance of many cellular processes. Although the enzymes that can synthesize and clear atRA in mammals have been identified, their tissue and cell-type specific roles are still not fully established. Based on the plasma protein binding, tissue distribution and lipophilicity of atRA, atRA partitions extensively to lipid membranes and other neutral lipids in cells.
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Department of Chemistry, University of Massachusetts, Amherst, MA 01003, USA.
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January 2025
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
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