Although adenosine is known to affect renal function through stimulating adenosine receptors, little is known about A1 receptors in human glomeruli. Thus, we attempted to identify the adenosine A1 receptor-cyclic AMP (cAMP) system in human glomeruli. Normal renal cortical tissues were obtained at nephrectomy of patients with renal cell carcinoma. Glomeruli were isolated using a graded sieving method or dissected manually under a stereomicroscope. Radioligand binding assay using 2-chloro-N-[3H] cyclopentyl adenosine ([3H]CCPA, an A1 agonist ligand) was performed at 30 degrees C for 90 minutes. Cyclic AMP (cAMP) produced in glomeruli was measured after incubation with different concentrations of N6-cyclohexyladenosine (CHA; A1 agonist) and a phosphodiesterase inhibitor. The specific binding was saturated within 60 minutes and reversible by adding 1 mM of theophylline. Scatchard plot analysis revealed a single class of binding site (Kd = 1.78 +/- 0.21 nM, Bmax = 271.7 +/- 35.8 fmol/mg protein). The specific binding was inhibited dose-dependently by various agents in an order suggesting A1 receptor specificity. CHA inhibited the production of cAMP in microdissected human glomeruli. This inhibitory effect was antagonized by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A1 antagonist). This is the first study revealing the presence of the A1 receptor-cAMP system in human glomeruli using a radioligand binding assay method and by measuring the cAMP production.