Sites of clonidine action to inhibit gut propulsion in mice: demonstration of a central component.
The role of central (supraspinal and spinal) and peripheral alpha-adrenoceptors in the regulation of gastrointestinal propulsion in the mouse was studied using clonidine, an alpha 2-adrenoceptor agonist. Clonidine produced a dose-dependent inhibition of propulsion when given intracerebroventricularly, intrathecally, or subcutaneously, but was most potent when given intracerebroventricularly. The antitransit effects of centrally given clonidine were antagonized by intracerebroventricular (i.c.v.) yohimbine, but higher doses were required when this antagonist was given peripherally. Whereas i.c.v. and s.c. administration of clonidine were effective in inhibiting gut transit in spinally transected mice, intrathecal (i.th.) administration of this agonist was not. A supraspinal site of clonidine action is suggested based upon (a) the higher central to peripheral potency of clonidine; (b) the greater potency of i.c.v., compared with s.c., administration of yohimbine in blocking i.c.v. clonidine; (c) the lack of effect of i.th. administration of clonidine in spinally transected mice; and (d) the reduced potency of i.c.v., but not s.c., administration of clonidine in spinally transected mice. Additionally, a peripheral site of clonidine action is suggested by (a) the lower potency of i.c.v. yohimbine in blocking s.c., compared with i.c.v., clonidine; (b) the lower potency of i.c.v. yohimbine in blocking i.c.v. clonidine in transected mice (compared with normal mice); (c) the equal potency of s.c. clonidine in slowing propulsion in normal and spinally transected mice; and (d) the equal potency of i.c.v. yohimbine in blocking s.c. clonidine in normal and spinally transected mice. These data in mice would thus support the concept that normal (peripheral) therapeutic administration of clonidine would affect gut motor function by interactions within the brain and directly at the level of the gut.
Jiang
Q
Q
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
Sheldon
R J
RJ
Porreca
F
F
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage* / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology* / Q000601:surgery; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin