Enhanced actions of nitric oxide in modulating gastrointestinal smooth muscle function during pregnancy

Abstract

• ENHANCED ACTIONS OF NITRIC OXIDE IN MODULATING GASTROINTESTINAL SMOOTH MUSCLE FUNCTION DURING PREGNANCY. S.N. Shah, J.M. Cuevas. A.J. Hobbs. E. Whan~,. L.J. I~,narro, S.W, Ashley & G. Chaudhuri. Departments of Pharrfiacology, Obstetrics & Gynecology and Surgery, UCLA School of Medicine, Los Angeles, CA 90024. Gastrointestinal (GI) disorders represent one of the roost frequent complaints experienced during pregnancy. Nitric oxide (NO) has reeently been shown to function as an inhibitory neurotransroitter in many regions of the GI tract, and to play an important role in regulating GI motility and smooth muscle reactivity. Therefore, a change in the physiological actions of NO may be causally linked to the GI problems observed during pregnancy. To investigate this possibility, the present study has compared the ability of NO to modulate smooth rouscle fimction in different regions of the GI tract in pregnant and non-pregnant animals. Smooth muscle preparations of both ileum and colon were examined using organ bath techniques. Tissues were taken from non-preguant (control), mid pregnant (11-13 days) and late-pregnant (18-20 days) feroale rats. In ileal preparations, eleclrical field stimulation (EFS) of the resting smooth muscle resulted in frequency-dependent contractions. Although there was no significant difference in EFS-induced contractions between control and mid-pregnant animals, responses to EFS in tissues from late-pregnant females were significantly reduced. Addition of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), was effective in potentiating EFS-induced contractions in control, mid-, and late-pregnant animals, hut was significandy more potent in late-pregnant tissue as compared to the other groups. In contrast to the ileum, EFS elicited frequency-dependent relaxations of the quiescent colonic smooth muscle. As observed in the ileum, in late-pregnant animals the response of the smooth rouscle to EFS was significantly different from that observed in control and roid-pregnant animals; in this instance the relaxant responses were markedly enhanced. In the colon, L-NAME reduced EFS-indnced relaxations in control, mid-, and late-pregnant animals. In this tissue however, L-NAME was significantly more potent at inhibiting relaxations in both midand late-pregnant animals as compared to controls. These data suggest that the control of GI smooth muscle function varies markedly between regions and may be significantly altered during pregnancy. Importantly, the role of NO (presumably released from NANC nerves) may contribute to this changed functioning. (Funded by NIH Grant HI..46843) GASTRIN GENE EXPRESSION IN HUMAN PANCREATIC AND COLON CANCERS, H. Sperling, J. Ishizuka. H.J . Kim, C.M. Townsend. Jr.. J.C. Thompson. Department of Surgery, University of Texas Medical Branch. Galveston, Texas. Gastrin stimulates growth of certain colon and pancreatic cancers; identification of gastrin gene expression in these cancers would suggest that gastrin may act in an autocrine fashion to regulate growth. The purpose of this study was to determine whether gastrin is expressed in colon and pancreatic cancers. Methods. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze three pancreatic (CAV, Panc1 and MIA PaCa-2) and two colon (LoVo and HCTIIt) cancer cell lines for gastrin gene expression. A human gastrinoma cell line (PT), that abundantly expresses gastrin, was used as a positive control. Results. RT-PCR demonstrated -280 bp fragment consistent with exon sequences of the gastrin gene