Loren Kline (PhD, University of Alberta)

Professor
7-58A MSB
University of Alberta
Edmonton, Alberta
Canada T6G 2H7

Tel:  780 492-3427
Fax: 780 248-1995

lkline@ualberta.ca


Research

Regulation of gallbladder motility
The gallbladder arises from a diverticulum on the ventral floor of the developing foregut. The intrinsic nerves of the gallbladder consist of ganglionated plexuses which arise from neural crest cells that colonize the gallbladder. These neural crest cells exhibit structural, neurochemical and physiological characteristics that make them distinct from the myenteric and submucosal plexuses of the gut. This suggests that the gallbladder may respond to different peptides than the gut or respond differently than the gut. Since the gallbladder also has a different function than the gut (i.e. the storage, concentration and delivery of bile into the duodenal lumen during digestion), an understanding of factors controlling motility -- both contraction and relaxation -- is required if the causes of abnormal conditions such as cholelithiasis (gallstones) are to be understood. Cholelithiasis affects 12% of the North American population, with an increasing incidence with advancing age. Considerable evidence suggests that abnormal gallbladder motility has a key role in most gallbladder conditions. The gallbladder does not relax, fill and empty completely when a meal is consumed. Mixing movements occur during between meal fasts to prevent supersaturation of bile in contact with the mucosa. This mixing could prevent gallstones and impairment of this mixing may occur. Work in the laboratory has shown that several agents may affect motility. It has been determined that calcitonin gene-related peptide (CGRP) relaxes cholecystokinin octapeptide-induced tension by stimulation nitric oxide (NO) synthesis, stimulating cAMP production, and acting on ATP-sensitive K+ channels. The effect of CGRP has been shown to be age-dependent. Pituitary adenylate cyclase-activating peptide (PACAP), parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) also affect gallbladder motility. The latter two hormones relax gallbladder contraction by acting through adenylate cyclase activation and cAMP production.

Tooth Replacement in the Iguana
The teeth in the common green iguana are replaced continuously in a highly ordered sequence. At intervals, new teeth are added to the tooth row. Work in the laboratory has shown that both the replacement and addition of new teeth are related to growth of the animal. Traditionally, studies have focused on teeth in the mandible due to uncertainty as to the effects of the maxillary-premaxillary suture on replacement. Work is in progress which examines maxillary tooth replacement.

Comparitive Physiological Studies
With the successful maintenance of iguanas in healthy, thriving conditions for long periods of time, an interest in expanding studies into comparative of physiology has developed. Work on factors affecting motility of the iguana gallbladder have been performed. In addition, work on vascular smooth muscle contractionis in progress.

Techniques
In vitro pharmacologic techniques have been used in all the smooth muscle experiments. In order to determine if intracellular Ca2+ fluxes modulate the actions of the various pharmacologic agents, intracellular Ca2+ has been measured using cultured cells and Fura-2.


Selected Publications