The relationship between variations in levels of serotonin acetyltransferase activity and cGMP content in cultured chick pineal glands

Abstract

1981)The rddionship between variations in levels of serotonin wtyltransferme activity and cQMP content in cultured chick pineal gbnds.Can. J. Bioclaem. 59,[593][594][595][596][597][598][599][600][601] Chick pineal glands cultwed in continuous darkness exhibited a circadian rhythm in 39951cyclic GMP (cGMP) content. cGMP content increased earlier and feu later than in glands incubated under diurnal lighting. A 66spike9e of further increase in c@MP content preceded s t a t of decline in acetyl-Col8:aqkHnine N-aeetyltransfemse (NAT) activity.Theophyuine or 4-(3-butoxy-4-methoxy~nzyl)-2-imdzldinne (c~mpoupnd Ro 20.1724) alone markedly stimulated increase of NAT activity in the dark, and retarded subsequent loss of activity either in the dark or in the photoperiod of a diurnal cycle of illurnhation. In constant darkness a combination of the two agents elicited greater increases of NAT than either alone and suppressed subsequent loss of activity for several hours. Under diurnal lighting conditions the combination was only slightly more effective than either alone. Compound Wo 20.1724 suppressed the precipitous loss of NAT activity seen when ghnds are transferred prematurely to the light. However, neither the rate or extent of loss of activity was greatly aEected by f Reophy Kne.Effects of theophylline and compound Wo 28.1724 upon levels of NAT activity appeared to be due primarily to effects upon the prowss(es) by which enzyme activity is lost. 'They could not be attributed solely to eaects upon pineal contents of cGMP and (or) 3',5kyclis AMP (CAMP).Tbeophylline alone was as effective as the drug combination in eliciting sand maintaining elevated pineal content of cGMP, but had little effect upon CAMP content. Compound Wo 20.1724 alone elicited large increases in pineal contents of both nucleotides but did not sustain them. Wainwright, S. D. & Wainwright, L. K. (8981) The relationship between variations in levels of serotonin acetyltransferase activity and cGMP content in cultured chick pineal glands.Can. 9. Bbchem. 59, 593-601 Dans les glandes pinCsales de poussins cultivCes dans une noirceur continue, Ia teneur en cGMP suit un rythme circadien. La teneur en cGMP augmente gllss t6t et tombe plus tard que dans les glandes incubCes B la lurmikre diurme. Un nouveaa "pic" d'augmentation du cGMP prkkde ie debut du d&Iin de 19activitC de l'adtyl-CoA:arylamine WP-acktyltransf6rase (NAT).

Relationship Between Cycles in Level of Serotonin N‐Acetyltransferase Activity and Cyclic GMP Content of Cultured Chick Pineal Glands

“…Effects of 1 mM compound SQ 20,009 were qualitatively similar to those of theophylline (Wainwright and Wainwright, 1981). Nevertheless, quantitative differences were noted between the effects of the two agents.…”

“…The response in constant darkness ( Fig. 2b) was indistinguishable from that with theophylline (Wainwright and Wainwright, 1981). Results for glands under diurnal lighting ( Fig.…”

“…Values are means +SD for either the number given in parentheses or three individual cub tures. For comparison we have included data for glands cultured with 1 mM theophylline from Wainwright and Wainwright (1981). Curves: (A) Control; (8) with 1 mM compound SQ 20,009;…”

“…However, there is no simple causal relationship between cyclic GMP content and NAT activity. Rather, they appear to be two independent cycles controlled by a common pineal "clock" (Wainwright and Wainwright, 1981).…”

“…Both the diurnal cycle and circadian rhythm in NAT activity found in vivo persist in vitro in chick pineal glands in organ culture (Binkley et al, 1978;Deguchi, 1979;Kasal et al, 1979;Wainwright and Wainwright, 1979). These cycles are paralleled by cycles in cycIic GMP content (Wainwright, 1980;Wainwright and Wainwright, 1981). However, there is no simple causal relationship between cyclic GMP content and NAT activity.…”