REGULAR ARTICLE Northern Elephant Seal Platelets: Analysis of Shape Change and Response to Platelet Agonists Cara L. Field, Naomi J. Walker and Fern Tablin Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California-Davis, 1321 Haring Hall, Davis, CA 95616, USA (Received 6 March 2000 by Editor N.N. Tandon; revised/accepted 23 October 2000) Abstract Blood platelets have a vital role in the main- tenance of normal mammalian hemostasis. Rapid pressure changes and temperatures lower than 20°C cause activation of human and terrestrial mammal platelets. Elephant seals are routinely subjected to pressures as high as 150 atm, yet do not suffer from the thrombotic effects of platelet activation associated with rapid decompression. We examined the ultrastructure of Northern elephant seal (Mirounga angustirostris) platelets and their functional and morphological response to various platelet agonists. Unstimulated ele- phant seal platelets are discoid cells, with a microtubule coil, randomly dispersed alpha and dense granules, and glycogen granules. There are well-defined areas of membranous invaginations that indicate the presence of an open canalicular system (OCS). Aggregometry was used to deter- mine the response of elephant seal platelets to various platelet agonists. Dose-dependent curves were generated for thrombin, collagen, and adenosine diphosphate (ADP). Platelet response to thrombin was dose-dependent and was max- imal at 2.5 U/ml. Platelets collected in sodium citrate had blunted responses to both ADP and collagen. ADP stimulation caused only reversi- ble, primary activation (shape change) at  5 mM, while platelets did not aggregate in response to any concentration of collagen. Platelets collected in sodium heparin did respond fully to both ADP and collagen. There was small, reversible shape change in response to ristocetin, but no response to epinephrine. Decreased sensitivity of elephant seal platelets to agonists may be a protective mechanism developed in response to rapid pressure changes and cold temperatures asso- ciated with adaptation to an extreme en- vironment. D 2001 Elsevier Science Ltd. All rights reserved. Key Words: Platelets; Platelet agonists; Aggregation; Elephant seals; Collagen B lood platelets from humans and other mammals are sensitive to physiological agonists such as thrombin, collagen, and adenosine diphosphate (ADP) [1]. Platelet activa- tion is induced to varying degrees, depending on both the concentration of the agonist and its mechanism of action. Upon stimulation, platelets change shape from discs to irregularly shaped cells with filopodia, then condense into small spheres, and aggregate [1]. Generally (see Cheryk et al. [2,3] for interesting exceptions), during activation platelet granules are centralized in the cell, fuse with the open canalicular system (OCS), and secrete their contents into the extra- cellular environment [4]. 0049-3848/01/$ ± see front matter D 2001 Elsevier Science Ltd. All rights reserved. PII S0049-3848(00)00392-3 Abbreviations: °C, degrees Celsius; ml, milliliters; mM, micro- molar; mg, microgram. Corresponding author: Dr. Cara L. Field, Department of Anat- omy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California-Davis, 1321 Haring Hall, Davis, CA 95616, USA. Tel: +1 (530) 752 1175; Fax: +1 (530) 752 7690; E-mail: <clfield@ucdavis.edu>. Thrombosis Research 101 (2001) 267 ± 277