Adenosine affects the calcium dynamics of rat portal vein R. S. Telang 1 , H. C. Tripathi 2 , S. K. Mishra 2 & V. Raviprakash 2 1 Department of Pharmacology and Toxicology, College of Veterinary and Animal Sciences, CSK HPKV, Palampur 176 062, HP and 2 Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122, UP, India Summary 1 The present study was carried out to characterize the effect of adenosine on calcium dynamics in the rat portal vein. Isolated portal vein of male albino rats was used as the experimental model as it exhibits autorhythmicity. Adenosine and its analogues 2-CAD, N 6 -CHA and NECA were used to characterize the type of adenosine receptor involved and 2-CAD was used along with adenosine throughout the other part of study to characterize the effect of adenosine on Ca 2+ dynamics. 2 Adenosine and its analogues were found to inhibit the spontaneous contractions of rat portal vein in a concentration-related manner. The order of potency was NECA > 2-CAD > N 6 -CHA > adenosine. Incubation of the tissue with CGS15943A, an adenosine receptor antagonist, had a per se enhancing effect on autorhythmicity. Adenosine and 2-CAD failed to reverse the contractile response produced by hypertonic KCl (80 or 30 mM). Whereas adenosine and 2-CAD effectively relaxed the tissues contracted with phenylephrine (10 )5 M). 3 Preincubation of the tissue with 2-CAD (10 )4 , 10 )5 or 10 )6 M) for 5 min raised the threshold concentration of CaCl 2 to evoke contractile response and also significantly increased the mean EC 50 values of CaCl 2 . Nifedipine was found to be more potent than 2-CAD on Ca 2+ channels. 4 The results of the present study suggest that the endogenous adenosine plays a significant role in producing vascular relaxation through the participation of A 2 receptor subtype. This effect may be due to its inhibitory effect on release of Ca 2+ from the intracellular stores. Further to this effect, 2-CAD had a major inhibitory effect on voltage-operated Ca 2+ channels compared with receptor-operated Ca 2+ channels. 5 It can be concluded that adenosine through its A 2 receptor produces vasorelaxant effect by interfering with the release of Ca 2+ from the intracellular stores coupled with influx of Ca 2+ from the extracellular sources. Keywords: adenosine, calcium, Ca 2+ channels, portal vein, ROCCs, VOCCs Introduction Purines (adenosine) and purine nucleotides (ADP and ATP) produce a wide range of pharmacological effects that are not directly related to their role in energy metabolism. Adenosine has been shown to participate in the regulation of physiological activ- ity in a variety of mammalian tissues and has been recognized as a homeostatic neuromodulator. This endogenous metabolite plays a major role in the regulation of coronary blood flow (Berne, 1980). Adenosine exhibits a vasodilatory property, for which the exact mechanism is still not com- pletely understood. Production of cAMP, cGMP, inhibition of Ca 2+ influx, modulation of voltage- operated Ca 2+ channels (VOCCs) and involvement of the protein kinase C-phospholipase C system have all been implicated as subserving the mech- anism of vasodilatation via activation of the A 2 adenosine receptor (Cushing, Brown, Sabouni & Mustafa, 1991a; Cushing, Makujina, Sabouni & Mustafa, 1991b). Calcium plays a critical role in excitation– contraction dynamics of vascular smooth muscle (VSM) and the main trigger for contraction is the elevation of intracellular Ca 2+ concentration ([Ca 2+ ] i ) (Somlyo, 1985). The regulation of [Ca 2+ ] i depends on both the entry and exit of Ca 2+ across 181 Autonomic & Autacoid Pharmacology, 23, 181–192 Ó 2003 Blackwell Publishing Ltd Correspondence: R. S. Telang