Kinetics of the enhancing effect produced by norepinephrine and terbutaline on the murine primary antibody response in vitro.

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.