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Beta-Adrenoceptors in the Guinea Pig Treated with Egg-Albumin
BETA-ADRENOCEPTORS TREATED Issei 'I'AKAYANAGI,
IN WITH
THE
GUINEA
PIG
EGG-ALBUMIN
Mineo MARUYAMA
and Keijiro TAKAGI
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-Ait, Tokyo 113, Japan Accepted November 8, 1976
Egg-albumin
is used as a sensitizing
tile present v,('FL vNCattempted
antigen
to determine
in experimental
whether
anaphylactic
shock.
In
or not affinities of drums to their re
ceptors were affected by a treatment of an animal with egg-albumin. Guinea pigs, weighing 350 to 400 g, were divided into two groups.
One group served
as control and these animals were given 3 ml/kg of saline solution giving s.c. daily x 3. other group was sensitized by antigen s.c. daily x 3 in a dose of 3 ml/kg. albumin in saline solution was used as the sensitizing antigen (1).
The
A 10% egg
Animals were sacrificed
after 3-4 weeks and the trachea, taenia coli, right atrium and uterus were isolated. tracheal preparation was handled by the method described by Takagi et al. (2).
The
The uterus
was isolated from guinea pigs given oestradiol benzoate (1 mg/kg) s.c. 24 hr before sacrifice. These smooth muscle preparations were suspended in a 30 ml organ bath filled with Locke Ringer solution kept at 37'C and gassed with a mixture of 95 % 02 and 5 % C02.
The
solution contained 147 mM NaCI, 5.1 mM KCI, 2.1 mM CaC12, 2.1 MM MgC12, 9.6 mM NaHCO3 and 2.8 mM glucose.
Isotonic responses of the tracheal preparation
coli were expressed as a percent of the maximum response to an agonist.
and taenia Strips of the
atrium and uterus were prepared under a I g initial tension for isometric recordings of responses.
Responses of the atrium to each concentration of 1-isoprenaline were expressed
as a percent of the maximum increase in tension and that of the uterus as inhibition (%) of spontaneous movement.
Cumulative dose response curves of the agonists were obtained
(3). Activity of the agonist was expressed as pD2-value which is the negative logarithm of a molar concentration required to produce half the maximum response (3). Activity of a competitive antagonist was also expressed as pA2-value (4). After the control dose response curve of the agonist had been obtained, the curve of the agonist in the presence of the com petitive antagonist was again obtained on the smooth muscle preparation which had been treated for 10 min beforehand with the competitive antagonist. The pA2-value was calcu lated from the parallel shift of the curve of the agonist, according to van Rossum (3). Two preparations of trachea and two pieces of taenia coli were prepared from all guinea
TABLE 1.
pD2 and pA2-values
and saline-treated
upper:
guinea
of drugs tested
value on the saline-treated
guinea pig. ( *:: significantly
on tissues isolated
from
the egg-albumin-treated
pigs
guinea
pig. lower:
value on the egg-albumin-treated
) : salt form of the drug. [ I : no. of experiments. different from the upper value at P,0.01
pigs treated with egg-albumin and one of each was used to determine whether or not an anaphylactic contraction could be observed by application of egg-albumin. All the tracheal preparations were contracted by 10-5 g/ml of egg-albumin and all the taenia coli contracted with 10-2 g/Inl. These observations coincided with findings of Yamaguchi (1) and Okamura and Shiina (5). The pD2-values of acetylcholine and histamine and pA2-values of atropine and diphen hydramine were not affected by the treatment with egg-albumin, suggesting that the treat ment did not induce any change in affinity of the drugs to acetylcholine receptors.
and histamine
On the other hand, treatment with egg-albumin significantly decreased the
pD2-value of 1-isoprenaline and the pA2-value of propranolol tested on the tracheal pre paration but not these values on the taenia coli, uterus and atrium. in Table 1.
Results are summarized
The present data clearly demonstrate that the affinity of drugs to beta-adrenoceptors is decreased only in the trachea by the treatment with egg-albumin.
Although further study is
required, our data support the view of Szentivanyi (6) that the beta-adrenoceptors are partial ly blocked in bronchial asthma. REFERENCES 1) YAMAGUCHI., M.: Fnlia pharinacol.japon. 60,588 (1964)(in Japanese); 2) TAKAGI, K., TAKA YANAGI, 1. ANDFUME,K.: Chem. Pharm. Bull. 6, 716 (1958); 3) VANRossuM, J.M.: Archs int. Pharmacody. Ther. 143, 299 (1963); 4) SCHILD,H.O.: Pharmacol. Rev. 9,242(1957); 5) OKANIURA, T. ANDSHIINA,Y.: Japan. J. Pharmacol. 22, 587 (1972); 6) SZENTIVANYI, A.: J. Allergv 42, 203 (1968)
IN WITH
THE
GUINEA
PIG
EGG-ALBUMIN
Mineo MARUYAMA
and Keijiro TAKAGI
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-Ait, Tokyo 113, Japan Accepted November 8, 1976
Egg-albumin
is used as a sensitizing
tile present v,('FL vNCattempted
antigen
to determine
in experimental
whether
anaphylactic
shock.
In
or not affinities of drums to their re
ceptors were affected by a treatment of an animal with egg-albumin. Guinea pigs, weighing 350 to 400 g, were divided into two groups.
One group served
as control and these animals were given 3 ml/kg of saline solution giving s.c. daily x 3. other group was sensitized by antigen s.c. daily x 3 in a dose of 3 ml/kg. albumin in saline solution was used as the sensitizing antigen (1).
The
A 10% egg
Animals were sacrificed
after 3-4 weeks and the trachea, taenia coli, right atrium and uterus were isolated. tracheal preparation was handled by the method described by Takagi et al. (2).
The
The uterus
was isolated from guinea pigs given oestradiol benzoate (1 mg/kg) s.c. 24 hr before sacrifice. These smooth muscle preparations were suspended in a 30 ml organ bath filled with Locke Ringer solution kept at 37'C and gassed with a mixture of 95 % 02 and 5 % C02.
The
solution contained 147 mM NaCI, 5.1 mM KCI, 2.1 mM CaC12, 2.1 MM MgC12, 9.6 mM NaHCO3 and 2.8 mM glucose.
Isotonic responses of the tracheal preparation
coli were expressed as a percent of the maximum response to an agonist.
and taenia Strips of the
atrium and uterus were prepared under a I g initial tension for isometric recordings of responses.
Responses of the atrium to each concentration of 1-isoprenaline were expressed
as a percent of the maximum increase in tension and that of the uterus as inhibition (%) of spontaneous movement.
Cumulative dose response curves of the agonists were obtained
(3). Activity of the agonist was expressed as pD2-value which is the negative logarithm of a molar concentration required to produce half the maximum response (3). Activity of a competitive antagonist was also expressed as pA2-value (4). After the control dose response curve of the agonist had been obtained, the curve of the agonist in the presence of the com petitive antagonist was again obtained on the smooth muscle preparation which had been treated for 10 min beforehand with the competitive antagonist. The pA2-value was calcu lated from the parallel shift of the curve of the agonist, according to van Rossum (3). Two preparations of trachea and two pieces of taenia coli were prepared from all guinea
TABLE 1.
pD2 and pA2-values
and saline-treated
upper:
guinea
of drugs tested
value on the saline-treated
guinea pig. ( *:: significantly
on tissues isolated
from
the egg-albumin-treated
pigs
guinea
pig. lower:
value on the egg-albumin-treated
) : salt form of the drug. [ I : no. of experiments. different from the upper value at P,0.01
pigs treated with egg-albumin and one of each was used to determine whether or not an anaphylactic contraction could be observed by application of egg-albumin. All the tracheal preparations were contracted by 10-5 g/ml of egg-albumin and all the taenia coli contracted with 10-2 g/Inl. These observations coincided with findings of Yamaguchi (1) and Okamura and Shiina (5). The pD2-values of acetylcholine and histamine and pA2-values of atropine and diphen hydramine were not affected by the treatment with egg-albumin, suggesting that the treat ment did not induce any change in affinity of the drugs to acetylcholine receptors.
and histamine
On the other hand, treatment with egg-albumin significantly decreased the
pD2-value of 1-isoprenaline and the pA2-value of propranolol tested on the tracheal pre paration but not these values on the taenia coli, uterus and atrium. in Table 1.
Results are summarized
The present data clearly demonstrate that the affinity of drugs to beta-adrenoceptors is decreased only in the trachea by the treatment with egg-albumin.
Although further study is
required, our data support the view of Szentivanyi (6) that the beta-adrenoceptors are partial ly blocked in bronchial asthma. REFERENCES 1) YAMAGUCHI., M.: Fnlia pharinacol.japon. 60,588 (1964)(in Japanese); 2) TAKAGI, K., TAKA YANAGI, 1. ANDFUME,K.: Chem. Pharm. Bull. 6, 716 (1958); 3) VANRossuM, J.M.: Archs int. Pharmacody. Ther. 143, 299 (1963); 4) SCHILD,H.O.: Pharmacol. Rev. 9,242(1957); 5) OKANIURA, T. ANDSHIINA,Y.: Japan. J. Pharmacol. 22, 587 (1972); 6) SZENTIVANYI, A.: J. Allergv 42, 203 (1968)