We previously reported that blood forms of Trypanosoma cruzi express alpha- and beta-adrenergic receptors and that binding of specific agonists to these receptors modifies the infective capacity of the parasite in vitro. The present study has revealed that the inhibitory effect of the beta-adrenergic agonist L-isoproterenol and the stimulatory effect of the alpha-adrenergic agonist L-phenylephrine are not produced when the parasite is subjected to prolonged exposure to otherwise effective doses of these agonists or when supraoptimal doses of these agonists are used. We refer to these phenomena as ‘desensitization’ because of their analogy with vertebrate cells becoming desensitized by prolonged exposure to, or relatively high concentrations of, adrenergic agonists. At a constant agonist concentration, T. cruzi desensitization was time-dependent and, when the time of parasite treatment with the agonists was not changed, the higher concentrations of the agonist tested were the most effective in producing desensitization. The reduced infectivity resulting from treatment with optimal doses of L-isoproterenol was accompanied by elevated levels of cyclic adenosine mono- phosphate (cAMP) which were not detectable when L-isoproterenol concentrations producing desensitization were used. This finding implicated cAMP as a likely second signal in the inhibitory mechanisms of this agonist. No significant change in cAMP was detectable in parasites treated with L-phenylephrine, leaving open the question about how optimal doses of this alpha-adrenergic agonist enhance T. cruzi infectivity. Parasite responsiveness to alpha- and beta-adrenergic agonists as well as the desensitization effects define a system which regulates infectivity and could be modified at the host tissue level by naturally occurring agonists.

Background and objective: The effects of clonidine and dopamine, both alone and together, on gastric tone were studied using an electronic barostat. This enabled volume changes to be measured in an intragastric bag with constant preset pressure.

Methods: Nine healthy male volunteers were each studied on two occasions in a randomized order. During each study period, a continuous infusion of dopamine was given, starting with a dose of 2.5 μg kg−1 min−1 and then increasing at 15-min intervals to 5.0 and 7.5 μg kg−1min 2 1. Clonidine 150 μg intravenously was given on one occasion during the infusion of dopamine (7.5 μg kg−1min−1) and on the other occasion 15 min before the dopamine infusion started.

Results: During dopamine infusion, the intragastric bag volume increased (gastric tone therefore decreasing) in a dose-related manner (total increase 290 6 114 mL). Clonidine given either during or before dopamine infusion did not influence the bag volume. When the dopamine infusion started 15 min after clonidine, the bag volume did not change until the infusion of dopamine reached 7.5 μg kg−1min−1(total increase 205 6 156 mL).

Conclusions: Dopamine reduced gastric tone in a dose-related manner, and clonidine did not influence gastric tone per se. If clonidine is given before dopamine, the effects of dopamine are reduced.