408
Brief Papers
Studies of Histamine Release from Pig Lung in vitro Induced by Extracts of Hemp Dust by B. WILLIAMSand P.J. NICHOLLS1 Welsh School of Pharmacy, UWIST, Cardiff, U.K.
The respiratory disease, byssinosis, occurs in certain textile mill workers exposed to dusts of cotton, soft hemp and flax. While there is considerable evidence that cotton dust contains a histamine-releasing agent which may contribute to symptoms of the disease (e.g. [1] and [2]), there has been less investigation of hemp and flax dusts. The present work examines the histamine-releasing activity of an aqueous extract of hemp dust from chopped pig lung in vitro [3]. The amount of water-soluble extractives is expressed in terms of the weight of dust from which it had been derived.
Results At every dust concentration examined histamine was released slowly from the lung, following a lag of 5 min, rising to a maximum at 25 rain. The release was pH and temperature-dependent, optimal conditions being at pH 7.4 and 37~ At pH 7.4 a dose-response relationship for histamine release was exhibited over the range 10-250 mg/ml of incubation medium and up to 20% of the total lung histamine was released at the maximally effective level. Using submaximally effective concentrations of hemp dust, a decrease of histamine released was observed when ~)B.W. is in receipt of a research grant from the Pharmaceutical Society of Great Britain.
incubation occurred in either a Ca/Mg-free medium or in the absence of glucose. The activity of both the hemp dust extract and compound 48/80 was inhibited by the presence in the medium of ninhydrin (10 -3 M), N-ethylmaleimide (10 -3 M), isoprenaline (10 -6 M), sodium salicylate (6 x 10-4 M), chromoglycate (2 x 10-4 M), theophyllin (5 x 10-4 M) and dibutyryl cyclic AMP (2 x 10-4 M).
Conclusion This evidence suggests that the histamine-releasing agent in hemp dust may act by a mechanism similar to that of compound 48/80.
Acknowledgments We thank Dr Antonio Barbero, Alicante, Spain, for the hemp dust.
References [1] J. EDWARDS, P. McCARTHY, M. MCDERMOTT, P.J. NICHOLLS and J.W. S~:ID~ORE, J. Physiol. Lond. 208, 63P (1970). [2] E. EVANS and P.J. NICItOLLS, Agents and Actions 4, 304 (1974). [3] P.J. NICHOLLS, E. EVANS,F. VALIC and E. ZUSKIN,Br. J. industr. Med. 30, 142 (1973).
Histamine Uptake and Metabolism in Smooth Muscle in vitro by L. ZILLETTI, S. FRANCHI-M1CHELIand C.A. MAGGI Institute of Pharmacology, University of Florence, Italy
Smooth muscle is able to capture and metabolize histamine, as we showed previously [ 1], in ileal longitudinal muscle of the guinea-pig. In this communication we report some later results, partly in ileal longitudinal muscle of the guinea-pig and partly in human bronchioli. We have found that theophylline facilitates histamine uptake in guinea-pig ileal longitudinal muscle which is not only dependent on the drug concentration, as we have previously shown, but also on the Concentration of histamine in the medium. In fact this facilitating effect of theophylline decreases with increasing histamine concentration in the medium. We have further demonstrated an uptake of histamine in fragments of human bronchus.
Methods These fragments of human bronchus were taken from lung specimens at operation, were free from bronchiectasis or from tumors and had a diameter of about 3 mm and length of 10 mm, weighing about 100 mg. These were suspended in Krebs-Henseleit liquid at 37~ containing histamine ring 14C. After washing with normal Krebs for 15 min the tissue was homogenized with 0.4 N HCIO 4 and 14C-
total radioactivity was determined in the clear supernatant. Analysis of histamine and its metabolic products was effected by a previously used technique [2, 3 ].
Results and discussion Fragments of human bronchioli firmly retained histamine 14C and the captured radioactivity was a direct function of the amine concentration in the medium within the limits of the concentrations used (10-7-10 -6 g/ml). The kinetics of histamine uptake seem to be asymptotic. At a concentration of 5 x 10-~ g/ml of histamine ~4C, the total 14C radioactivity taken up in 30 min consisted of 14% of unmodified histamine, 26% of methylhistamine and 60% of acid metabolites. This uptake and metabolism of histamine may have a bearing upon the anaphylactic reaction in human bronchus.
References [11 L. ZILLETTE and S. FP,ANCHI-MICHELI, Agents and Actions 5,470 (1976). [2] S.H. SNYDER, J. AXELROD and H. BAUER,J. Pharmac. 144, 373 0954). [3] R.W. SCHAVER, in: Methods of Biochemical Analysis (Ed. D. Glick; Interscience, New York, 196g), p. 273.
Brief Papers
Studies of Histamine Release from Pig Lung in vitro Induced by Extracts of Hemp Dust by B. WILLIAMSand P.J. NICHOLLS1 Welsh School of Pharmacy, UWIST, Cardiff, U.K.
The respiratory disease, byssinosis, occurs in certain textile mill workers exposed to dusts of cotton, soft hemp and flax. While there is considerable evidence that cotton dust contains a histamine-releasing agent which may contribute to symptoms of the disease (e.g. [1] and [2]), there has been less investigation of hemp and flax dusts. The present work examines the histamine-releasing activity of an aqueous extract of hemp dust from chopped pig lung in vitro [3]. The amount of water-soluble extractives is expressed in terms of the weight of dust from which it had been derived.
Results At every dust concentration examined histamine was released slowly from the lung, following a lag of 5 min, rising to a maximum at 25 rain. The release was pH and temperature-dependent, optimal conditions being at pH 7.4 and 37~ At pH 7.4 a dose-response relationship for histamine release was exhibited over the range 10-250 mg/ml of incubation medium and up to 20% of the total lung histamine was released at the maximally effective level. Using submaximally effective concentrations of hemp dust, a decrease of histamine released was observed when ~)B.W. is in receipt of a research grant from the Pharmaceutical Society of Great Britain.
incubation occurred in either a Ca/Mg-free medium or in the absence of glucose. The activity of both the hemp dust extract and compound 48/80 was inhibited by the presence in the medium of ninhydrin (10 -3 M), N-ethylmaleimide (10 -3 M), isoprenaline (10 -6 M), sodium salicylate (6 x 10-4 M), chromoglycate (2 x 10-4 M), theophyllin (5 x 10-4 M) and dibutyryl cyclic AMP (2 x 10-4 M).
Conclusion This evidence suggests that the histamine-releasing agent in hemp dust may act by a mechanism similar to that of compound 48/80.
Acknowledgments We thank Dr Antonio Barbero, Alicante, Spain, for the hemp dust.
References [1] J. EDWARDS, P. McCARTHY, M. MCDERMOTT, P.J. NICHOLLS and J.W. S~:ID~ORE, J. Physiol. Lond. 208, 63P (1970). [2] E. EVANS and P.J. NICItOLLS, Agents and Actions 4, 304 (1974). [3] P.J. NICHOLLS, E. EVANS,F. VALIC and E. ZUSKIN,Br. J. industr. Med. 30, 142 (1973).
Histamine Uptake and Metabolism in Smooth Muscle in vitro by L. ZILLETTI, S. FRANCHI-M1CHELIand C.A. MAGGI Institute of Pharmacology, University of Florence, Italy
Smooth muscle is able to capture and metabolize histamine, as we showed previously [ 1], in ileal longitudinal muscle of the guinea-pig. In this communication we report some later results, partly in ileal longitudinal muscle of the guinea-pig and partly in human bronchioli. We have found that theophylline facilitates histamine uptake in guinea-pig ileal longitudinal muscle which is not only dependent on the drug concentration, as we have previously shown, but also on the Concentration of histamine in the medium. In fact this facilitating effect of theophylline decreases with increasing histamine concentration in the medium. We have further demonstrated an uptake of histamine in fragments of human bronchus.
Methods These fragments of human bronchus were taken from lung specimens at operation, were free from bronchiectasis or from tumors and had a diameter of about 3 mm and length of 10 mm, weighing about 100 mg. These were suspended in Krebs-Henseleit liquid at 37~ containing histamine ring 14C. After washing with normal Krebs for 15 min the tissue was homogenized with 0.4 N HCIO 4 and 14C-
total radioactivity was determined in the clear supernatant. Analysis of histamine and its metabolic products was effected by a previously used technique [2, 3 ].
Results and discussion Fragments of human bronchioli firmly retained histamine 14C and the captured radioactivity was a direct function of the amine concentration in the medium within the limits of the concentrations used (10-7-10 -6 g/ml). The kinetics of histamine uptake seem to be asymptotic. At a concentration of 5 x 10-~ g/ml of histamine ~4C, the total 14C radioactivity taken up in 30 min consisted of 14% of unmodified histamine, 26% of methylhistamine and 60% of acid metabolites. This uptake and metabolism of histamine may have a bearing upon the anaphylactic reaction in human bronchus.
References [11 L. ZILLETTE and S. FP,ANCHI-MICHELI, Agents and Actions 5,470 (1976). [2] S.H. SNYDER, J. AXELROD and H. BAUER,J. Pharmac. 144, 373 0954). [3] R.W. SCHAVER, in: Methods of Biochemical Analysis (Ed. D. Glick; Interscience, New York, 196g), p. 273.
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