SPINAL &BRAIN MODULATION OF GASTROINTESTINAL MOTILITY

It is recently evident that the central nervous system (CNS) exerts
important regulatory influences on gastrointestinal (GI) motility.
CNS neuropeptides appear to be especially important in central
regulation of motility. Certain of the centrally-distributed
"brain-gut" neuropeptides administered exogenously have dramatic
effects in the motility and reflexes of the GI tract. The specific
sites or mechanisms through which these peptides affect the gut
have not been determined. Neuropeptides can act at a discrete
sites in affecting GI motor function: the brain the neurons of the
enteric nervous system, the smooth muscle of the gut, and, as only
very recently demonstrated, the spinal cord. It is the hypothesis
of this proposal that the "brain-gut" peptides act through
chemosensitive sites in the brain and spinal cord to serve as
physiological or pharmacological modulators of GI motility. We
propose to focus our studies on the central effects of mammalian
bombesin agastrin releasing peptide; GRP), corticotropin releasing
hormone (CRF) and certain opioid neuropeptides on (a) ongoing and
(b) evoked reflex activity of the gut. Our approach will initially
involve administration of neuropeptides into the brain and into the
spinal subarachnoid space to define the chemosensitive sites
fundamentally involved in the control of GI motility. The
endpoints to be studied are all standard in our laboratory and
include determination of gastric emptying and small and large bowel
transit, stomach and intestinal intraluminal pressure in the rat
as will as GI transit in the mouse. In addition, a recently
developed model proposed for study is the evoked gastrocolic reflex
in the rat. The major techniques that will be employed to dissect
the peptidergic pathways that control the gut include: (a)
microinjections into specific brain locations and cord levels and
(b) transection of the spinal cord at various levels so that the
influence of the sympathetic or parasympathetic gut innervation can
be determined. Our recent work provides evidence that peptide
sensitive sites in the spinal cord can be distinguished
anatomically, pharmacologically and functionally from those in the
brain. Knowledge of the sites and functions of the neuronal
"brain-gut" peptides will provide new information about central
nervous system-gut interactions.