Structure and conformational properties of the Leu-callatosatin 4 neuropeptide

SMOKING

AND PANCREATIC

DISORDERS:

Chowdhury, Parimal; Rayford, Phillip L University of Arkansas for Medical Sciences,

ROLE OF NICOTINE

USA

Cigarette smoking plays a significant role in the development of various pancreatic diseases in humans. With the increased consumption of cigarettes two major pancreatic diseases, pancreatitis and pancreatic cancer, appear to be most common in cigarette smokers. We believe that nicotine, an addictive component and a pro-carcinogen in cigarette smoke, plays an important role in the etiology of these pancreatic diseases in cigarette smokers. To evaluate a linkage between nicotine consumption and the induction of these pancreatic diseases, a rodent model was developed in our laboratory to study systematically the effect of graded doses of nicotine on the structure and function of the exocrine pancreas. Animals in our study were exposed to nicotine via various routes of administration for hours to months. In most studies, exposure of rats to nicotine resulted in gross structural changes of the exocrine pancreas. These changes were associated with suppression of pancreatic function and activation of a proto-oncogene, Ha-ras, in pancreatic acinar cell. Mechanistic studies examining receptor and post-receptor regulated pathways of exocytotic secretion implicated calcium as a leading second messenger for alteration of pancreatic secretions and for the induction of cytotoxic injury of the pancreas by nicotine. Our data suggest that the effects of nicotine on the pancreas following cigarette smoking may be direct and most likely activate post-receptor mediated modulation of exocrine pancreatic secretion leading to cellular injury. This animal model will be used in future studies to further determine the role of nicotine in pancreatic pathophysiology.

STRUCTURE AND CONFORMATIONAL NEUROPEPTIDE

PROPERTIES

OF THE LEU-CALLATOSATIN

4

Aliev, Dshavanchir Ismet; Velieva, Lala I; Alieva, lrada N; Godjaev, Niftali M Baku State University, Azerbaijan The spatial structure and conformational peculiarities of the Leu-callatostatin 4 molecule isolated from nervous tissues of the blowfly Calliphora vomiforia have been studied by the theoretical conformational analysis method. Leu-callatostatin, designated callatostatin 4, has a sequence of amino acid residues AsnArg-Pro-Tyr-Ser-Phe-Gly-Leu-NH2, that show C-terminal pentapeptide fragment homology to the allatostatins of cockroaches. Calculation experiment was carried out using the semiempirical potential functions described all kind of atom-atomic interactions. The full conformational energy of molecule represented as a sum of independent contributions of non-valent, electrostatic, torsional interactions and energy of hydrogen bonds formation is defined by the minimization procedure. The energies and geometrical parameters a number of low-energetical conformation states Leu-callatostatin 4 molecule have been established. According to the calculation results the lowest energy conformer namely the global conformer has a rigid alpha-helical structure on the C-terminal pentapeptide fragment of the Leu-callatostatin 4 molecule. It is found that the strong interactions between Arg2 residue and Tyr4, Ser5, Phe6 are characteristic for all the low energy structures of neuropeptide. Arg2 makes an important contribution (-4,2 kcal/mol in average) towards the electrostatic interaction to the stabilization of the low-energy structures. The represented data may serve as the basis for investigation of the structure-function relationship of Leu-callatostatin 4 molecule to reveal the mechanism of the action of this neuropeptide.