Pharmacodynamics of salmon calcitonin in humans: New markers of pharmacological activity
- 32 Downloads
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 p02 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.
Key wordsSalmon calcitonin pharmacodynamics adenosine pO2 IM dosing nasal spray dosing cytosolic calcium neutrophils platelets lymphocytes
Unable to display preview. Download preview PDF.
- 1.MacIntyre I, Craig RK (1982) Molecular evolution of the calcitonins. In: Fink RG, Whalley LJ (eds) Neuropeptides: basic and clinical aspects. Proceedings of the 11th Pfizer International Symposium. September 1981. Churchill Livingstone, pp 255–258Google Scholar
- 2.Guttmann S (1981) Chemistry and structure-activity relationship of natural and synthetic calcitonin. In: Pecile A (ed) Calcitonin 1980. Proceedings International Symposium Milan 1980. Excerpta Medica Int Congr Ser 540: 11–24Google Scholar
- 5.Azria M (1989) The calcitonins. Physiology and pharmacology. Karger, Basel, pp 1–152Google Scholar
- 6.Caniggia A, Gennari C (1987) Timing of the effects of bPTH (1–34), pCT and sCT on calcium and cAMP in man. Calcif Tissue Res suppl 2: 318–322Google Scholar
- 7.Gennari C, Chierichetti SM, Vibelli C, Francini G, Maioli E, Gonnelli S (1981) Acute effects of salmon, human and porcine calcitonin on plasma calcium and cyclic AMP levels in man. Curr Ther Res 30: 1024–1032Google Scholar
- 8.Berne RM (1985) Criteria for the involement of adenosine in the regulation of blood flow. In: Paton DM (ed) Methods in pharmacology, Plenum Press, New York, pp 331–336Google Scholar
- 9.Sparks HV Jr, Gorman MW (1987) Adenosine in the local regulation of blood flow: current controversies. In Gerlach E, Becker BF (eds) Topic and perspectives in adenosine research. Springer Berlin Heidelberg New York, pp 406–415Google Scholar
- 10.Perr HM, Kahn AJ, Chappel JC, Kohler G, Teitelbaum SL, Peck WA (1983) Calcitonin response in circulating human lymphocytes. Endocrinology 113: 1568–1573Google Scholar
- 11.Grynkievicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440–3450Google Scholar
- 13.Singer FR, Rude RK, Mills BG (1976) Studies of the treatment and aetiology of Paget's disease of bone. In: MacIntyre I (ed) Human calcitonin and Paget's disease. Proceedings of an International Workshop, London, April 1976, Huber, Bern Stuttgart Toronto, pp 93–110Google Scholar
- 14.Vattimo et al. (unpublished data)Google Scholar
- 15.Shepherd AP, Riedel GL, Maxwell LC, Kiel JW (1984) Selective vasodilators redistribute intestinal blood flow and depress oxygen uptake. Am J Physiol 247: 377–384Google Scholar
- 16.Christopher YP, Choong C, Gary S, Roubin G, Wei-Feng Shen M, Phillip J, Harris P, Kelly D (1985) Effects of nifedipine on systemic and regional oxygen transport and metabolism at rest and during exercise. Circulation 71: 787–796Google Scholar
- 18.Laghi Pasini F, Capecchi PL, Orrico A, Ceccatelli L, Di Perri T (1985) Adenosine inhibits polymorphonuclear in vitro activation: a possible role as an endogenous calcium entry blocker. J Immunopharmacol 7: 203–215Google Scholar
- 19.Laghi Pasini F, Capecchi PL, Pasqui AL, Ceccatelli L, Di Perri T, Valensin G, Gaggelli E (1990) Adenosine blocks calcium entry into activated neutrophils and binds to flunarizine-sensitive calcium channels. Immunopharmacol Immunotoxicol 12: 77–93Google Scholar
- 21.Kishikawa T, Shimazawa E, Ogata E (1982) Involvement of calcium in calcitonin induced stimulation of glycolysis in rat kidney in situ. Endocrinol Japan 29: 149–157Google Scholar
- 22.Borle AB (1983) Calcitonin and the regulation of calcium transport and of cellular calcium metabolism. Triangle 2: 75–90Google Scholar
- 24.Pecile A, Olgiati VR, Sibilia V (1983) Attività analgesica di calcitonina di diversa origine. In: Gennari C, Segre G (eds) The effects of calcitonin in man. Proceedings 1st International Workshop, Florence 1982, Masson Paris, pp 205–211Google Scholar
- 28.MacIntyre I (1988) The radioimmunoassay of calcitonin and the calcitonin gene peptide: relationship to the biological activity. In: Mazzuoli GF (ed) Calcitonin '88, Rome March 26–27 1988. Si Stempa Medica s. p. a., S. Donato Milanese, pp 9–14Google Scholar