Biochemical Pharmacology. Vol. 33, No. 4. pp. 539-542, 1984. Printed in Great Britain. 0006295~84 $3.00 + 0.00 01984 Pergamon Press Ltd. EFFECT OF SOME MONOAMINE OXIDASE INHIBITORS AND CYCLIC-AMP ON PLASMA FIBRINOGEN LEVEL OF RATS JAYASRI SARKAR, AMIT ROY,TAPATI CHAXERJEE and ASOKE G. DATTA* Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700 032, India zyxwvutsrqponmlk (Received 7 July 1983; accepted 15 September 1983) Abstract-In viuo administration of short acting or long acting inhibitor of monoamine oxidase elevates plasma fibrinogen level in rats. These inhibitors cannot elevate plasma fibrinogen level in rats pretreated with p-chlorophenyl alanine and cu-methyl-meta-tyrosine, inhibitors of catecholamine and serotonin formation respectively. However, administration of epinephrine or serotonin under the above experi- mental condition elevates fibrinogen level indicating rise of biogenic monoamine, even for a short period, is a good stimulus for increase of plasma fibrinogen. Dibutyryl cyclic-AMP (c-AMP) also elevates fibrinogen level and shows additive effect with theophylline or serotonin. Earlier reports from our laboratory show that administration of iproniazid decreased the plasma monoamine oxidase (MAO) and increased the fibri- nogen level in both rabbits and rats [l]. We have observed that administration of some biogenic amines like epinephrine, serotonin, tyramine, etc. to rats and rabbits also elevated the plasma fibri- nogen level [ 11. It is well established that liver is the site of synthesis and secretion of fibrinogen [2,3] and clorgyline (N-methyl N-propergyldichlorophenoxy-propylam- ine) and pargyline (N-methyl-N-2-propynyl-benzyl- amine) are known to be tissue MAO inhibitors [4]. Thus, it was thought interesting to study the effect of these inhibitors on liver MAO and plasma fibri- nogen level and the results show that these inhibitors did elevate the plasma fibrinogen. However, it is still not clear whether the elevation of fibrinogen is due to a direct effect of MAO inhibitors or the effect is mediated through accumulated biogenic mono- amines. In order to have some idea on this question two other compounds, which, unlike reserpine, deplete monoamine by inhibiting their formation, were tried in our experiments. DL-p-Chlorophenyl- alanine (PCP) reduces tissue serotonin by inhibiting tryptophan hydroxylase [5] and n+methyl-m-tyrosine ( (u-MMT) lowers tissue catecholamines by inhibiting aromatic amino acid decarboxylase [6], and also possibly by producing false transmitter [7]. The effect of harmaline and monoamines on rats pretreated with these two compounds are quite interesting and the results are incorporated in this communication. In terms of duration of effect, MAO inhibitors have been classified in (i) long-acting type like par- gyline and (ii) short-acting type like harmaline (l- methyl-7-methoxy-3,4-dihydrocarboline) [4]. Results obtained on the effects of pargyline and harmaline on the MAO activity and plasma fibri- nogen level in normal rats are also included. * To whom correspondence should be addressed. A number of amines seem to produce similar effect on plasma fibrinogen level [I] and it appears that there might be a common mode of action for all these monoamines and, if so, whether it is through c-AMP. Since epinephrine is known to elevate c- AMP level in liver [8], attempts have, therefore, been made to find out whether there is any involve- ment of c-AMP in this process. MATERIALSAND METHODS Serotonin, pargyline, theophylline, DL-p-chloro- phenylalanine, Lu-methyl-m-tyrosine, epinephrine and dibutyryl c-AMP were purchased from Sigma Chemical Company and clorgyline was procured from May and Baker, U.K. Treatment of rats Female rats 100-120 g of the Wister Albino IICB inbred strain from the Institute colony were used. MAO inhibitors and theophylline were injected intraperitonially whereas serotonin, epinephrine and dibutyryl c-AMP were administered intramuscularly. The rats were killed at definite times and blood and liver were collected. In our previous report [I] rats were pretreated with reserpine to increase the sen- sitivity towards amine but in the present one, reser- pine treatment was omitted to avoid complication. Assay of MAO Rat liver mitochondria was prepared according to the method of Gross0 and Gawienowski [9]. Minced livers were homogenised in 3 vol. of 0.32 M sucrose medium containing 0.1 mM EDTA at pH 7.0 by a motor-driven Potter-Elvehjem homogenizer with Teflon pestle. The homogenate was diluted to 10 vol. and centrifuged at 3000 g for 3 min in a Sorval Model RC 2-B refrigerated centrifuge. The supernatant was again centrifuged at 35,000 g for 15 min. The result- ing pellet was washed twice with 0.32 M sucrose, resuspended in 0.32 M sucrose and was used as the enzyme. The assay of liver MAO was carried out 539