Towards identifying optimal doses for alpha-2 adrenergic modulation of colonic and rectal motor and sensory function.
BACKGROUND
Visceral sensation and motility are important in functional gut disorders and are partly controlled by adrenergic innervation.


OBJECTIVE
To characterize the alpha2-adrenergic control of motor and sensory function of descending colon and rectum.


METHODS
In 32 healthy volunteers, we assessed compliance, fasting and postprandial tone, and sensations of gas, urgency and pain during phasic distentions. Each subject received one agent at clinically approved doses: clonidine (0.05, 0.1, 0.2 or 0.3 mg p.o. ); or the alpha2 antagonist yohimbine (0.0125 mg, 0.05 mg, 0.125 mg or 0.2 mg intravenously and infusion over 2.5 h).


RESULTS
Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency. Clonidine showed large pairwise differences in sensation and motility between 0.05 and 0.1 mg doses, which did not interfere with the colon's motor response to feeding. Conversely, yohimbine dose-dependently altered the compliance curve, increased tone and sensations of gas, pain and urgency. Drug effects in the colon were more marked at low distensions; alpha2 modulation of rectal sensation was observed at all levels of distension.


CONCLUSIONS
alpha2-adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of alpha2 agents in disease states.
Malcolm
A
A
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester 55905, USA.
Camilleri
M
M
Kost
L
L
Burton
D D
DD
Fett
S L
SL
Zinsmeister
A R
AR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D003106:Colon / Q000294:innervation* / Q000502:physiology; D003109:Colonic Diseases, Functional / Q000503:physiopathology; D005260:Female; D005740:Gases; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D008297:Male; D010146:Pain / Q000503:physiopathology; D010465:Perception; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012007:Rectum / Q000294:innervation* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D005740:Gases; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D003000:Clonidine