Individual sympathetic varicosities possess different sensitivities to alpha 2 and P2 receptor agonists and antagonists in mouse vas deferens

1 The diversity of alpha(2) and purinergic autoreceptor actions on action potential evoked calcium transients in single varicosities has been investigated using the calcium indicator Oregon Green 488 BAPTA-1. 2 During long trains of impulses (10 Hz for 30 s), the change in calcium concentration in varicosities from its resting level (Delta[Ca2+](v)) increased in many varicosities during the first 3 a of stimulation before reaching a plateau. 3 The alpha(2) adrenoceptor agonist clonidine (1 mu M) decreased Delta[Ca2+](v) by over 40% during short trains (five impulses at 5 Hz) in most varicosities, although some were unaffected. The alpha(2) adrenoceptor antagonist idazoxan (2 mu M) increased the Delta[Ca2+](v) plateau following long trains in most varicosities. Hence, most varicosities possess alpha(2) adrenoceptors which are activated when noradrenaline accumulates extracellularly. 4 During long trains of impulses, the P-2y-purinergic receptor agonist 2-methyl-thio-ATP (100 mu M) decreased Delta[Ca2+](v) plateau by about 50% in most varicosities; alpha,beta-methylene ATP (100 mu M) decreased it by about 50% in a minority of varicosities; adenosine (200 mu M) had no significant effect. Suramin (100 mu M) increased the Delta[Ca2+](v) during all stimulus protocols in most varicosities, suggesting that ambient ATP modulates Delta[Ca2+](v) responses. The P-2y receptor antagonist reactive blue (100 mu M) affected a minority of varicosities. Given that most varicosities respond to suramin, other Pt receptor subtypes are probably present. 5 The ATP ectoenzyme antagonist ARL67157 (50 mu M) decreased the plateau Delta[Ca2+](v) during long trains in complete strings of varicosities but not in others. 6 The present technique indicates that varicosities have diverse autoreceptor utilization.