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[Ca(2+)](v)) increased in many varicosities during the first 3 s of stimulation before reaching a plateau. 3. The alpha(2) adrenoceptor agonist clonidine (1 microM) decreased Delta[Ca(2+)](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 microM) increased the Delta[Ca(2+)](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 microM) decreased Delta[Ca(2+)](v) plateau by about 50% in most varicosities; alpha,beta-methylene ATP (100 microM) decreased it by about 50% in a minority of varicosities; adenosine (200 microM) had no significant effect. Suramin (100 microM) increased the Delta[Ca(2+)](v) during all stimulus protocols in most varicosities, suggesting that ambient ATP modulates Delta[Ca(2+)](v) responses. The P(2y) receptor antagonist reactive blue (100 microM) affected a minority of varicosities. Given that most varicosities respond to suramin, other P(2) receptor subtypes are probably present. 5. The ATP ectoenzyme antagonist ARL67157 (50 microM) decreased the plateau Delta[Ca(2+)](v) during long trains in complete strings of varicosities but not in others. 6. The present technique indicates that varicosities have diverse autoreceptor utilization.