Abstract

Experiments were performed to determine the minimal drug exposure time required for norepinephrine and a relatively selective beta-2 adrenoceptor agonist to produce a maximal enhancing effect on the murine primary antibody response in vitro. The antibody response was determined by counting the number of spleen cells producing immunoglobulin M antibody directed against sheep erythrocytes 5 days after exposure of spleen cells to antigen and drugs. Norepinephrine (10(-5) M) or terbutaline (10(-5) M) were added to mouse spleen cell suspensions at the time of immunization with sheep erythrocytes on day 0. Phentolamine (10(-5) M) and/or propranolol (10(-6) M) were added to the spleen cell cultures to block adrenoceptor activation either at the time of agonist exposure (time = 0 hr) or at various times after agonist exposure (time = 15 min-96 hr). The addition of adrenoceptor antagonists at times after agonist exposure allowed for determination of the minimal time required for adrenoceptor activation to produce a maximally enhanced antibody response. Norepinephrine and terbutaline produced a maximally enhanced antibody response, as measured 5 days later, after 5 to 6 hr of agonist exposure before the addition of the antagonists. Addition of the antagonists at times later than 5 to 6 hr after agonist had no effect on the maximal antibody response. When antagonists were added before this time, the magnitude of the enhancing effect attained was time-dependent. These results indicate that early adrenoceptor activation in vitro is responsible for initiating events which culminate in an enhanced primary antibody response measured a number of days after drug exposure.