In Vivo and In Vitro Manifestations of Adrenergic Blockade inBordetella pertussis-vaccinated Mice

Abstract

The in vivo metabolic events which follow the administration of epinephrine, norepinephrine, or isoproterenol were examined in normal, Bordetella pertussisvaccinated, and a and adrenergically blocked mice. The normal hyperglycemic response to epinephrine was suppressed in all experimental groups. The pertussissensitized and ,B-blocked animals produced similar split patterns of altered response not duplicated by the a-blocking compounds. Those catecholamines that normally increase free fatty acids and lactic acid in the circulation failed to do so in the pertussis-sensitized and fl-blocked animals; the inhibition of free fatty acid mobilization was also demonstrated with adipose tissue incubated in vitro. An extract of the pertussis organism added to incubation media prevented the catecholamine-induced free fatty acid response. The epinephrine-stabilizing effect of bovine serum albumin (Cohn-fraction V) was observed. The results of these studies further emphasize a correlation between pertussis-sensitized and fl-adrenergically blocked mice. MATERIALS AND METHODS Mice. Female, CFW, white mice obtained from Carworth Farms were employed in the present study. They were housed in groups not exceeding 50 in number and were allowed food and water ad libitum. At the time of the experiments, the animals weighed between 18 and 20 g. Pertussis vaccine and extract. Fluid vaccine, a suspension of killed B. pertussis organisms, lot BP-0317, was supplied by Eli Lilly & Co., Indianapolis, Ind. This suspension was diluted 1:2 in sterile, nonpyrogenic, physiological saline. To establish the sensitive state, the animals were injected intraperitoneally with 0.5 ml of this suspension and were used in the experiments 5 days later. A soluble extract of pertussis organisms containing the histamine sensitizing factor was kindly furnished by J. Munoz, Public Health Service, Hamilton, Mont. Drugs. The following materials were purchased commercially from Winthrop Laboratories, New York, N.Y.: epinephrine, synthetic, as bitratrate (Suprarenin) containing 1 mg of base per ml, and isoproterenol HCI (Isuprel) containing 0.2 mg of 804

Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis.

“…Epinephrine Refractory Hypoglycemia. It is known that injection of B. pertussis cells into experimental animals results in hypoglycemia and a decreased responsiveness to epinephrine as measured by a lack of elevation of blood sugar after injection of the catecholarnine (18)(19)(20). Table VI presents epinephrine in mice which had received between 0.1 and 1.0/~g of LPF and only a minimal response, compared to that found in control mice, in those which had received 0.02/~g of LPF.…”

Histamine-sensitizing factors from microbial agents, with special reference to Bordetella pertussis.

“…HSF does not seem to interfere with production of adrenal hormones but rather to prevent the normal action of epinephrine by "blocking" the f3-adrenergic receptors needed for some of the activities of epinephrine. Much support was given to this view when Fishel and co-workers showed that fl-adrenergic blocking agents mimic the effect of HSF and that HSF produces many metabolic disturbances associated with 3-adrenergic activity (58-60, 92,228,233). If HSF actually blocks the f-adrenergic receptors, this blocking effect must be long lasting, and as a result it may produce many other modifications in the animal.…”

Bordetella pertussis-induced Alteration of the Normal Hyperglycemic Response of Mice to 3′,5′-Adenosine Phosphate

“…On the other hand, there were feati duced hyperglycemia in mice which aI differ from those noted in other spi example, other investigators have repoi crease in blood glucose in Abut not 4 gically blocked rats after 3' , 5'-AMP a tion, although both groups were unres epinephrine (13). The present studic strated the ineffectiveness of the nuc mice, regardless of the type of adrenergi or pertussis-sensitization (Tables 1, 3 difficulties associated with any interpr these data, including variations in exj conditions, assignment of metabolic specific receptors, differences in permi various tissues to the nucleotide, and th nature of the hyperglycemic responm several points seem worthy of con There are a number of observations whi that, in mice and rats at least, catec induced hepatic glycogenolysis is a cc of a-receptor activation (8,22). emphasis is placed on other factors M -AMP on the tributions to hyperglycemia have been recently s-sensitized summarized (7).…”

“…Based primarily upon the failure of epinephrine to elicit the normal hyperglycemic response and the duplication of the histamine sensitivity by adrenergic blocking substances, it has been suggested that the histamine phenomenon is associated with a lesion in the autonomic nervous system (6). More specifically, it would appear that, of the two types of adrenergic receptors, the pertussis organism possesses a component which combines with the /3 type and renders them unresponsive to normal transmitter substances, such as epinephrine or norepinephrine or both (4,5,8).…”