Alpha-adrenoreceptor modulation of neurally evoked circular muscle responses of the guinea pig stomach.
The effects of alpha-adrenergic agonists on transmural-evoked motor responses were investigated in guinea pig gastric corpus in vitro, using preparations stripped of mucosa and orientated to record changes in circular muscle tension. Three tetrodotoxin-sensitive components to a 10 s burst of transmural stimulation could be distinguished: an initial 'on' contraction, an 'off' contraction and a transient relaxation. The 'on' response was blocked by atropine (0.1 microM), while the 'off' response and relaxation were unaffected at this dose. A submaximal dose of acetylcholine was used to assess the sensitivity of the preparation. The alpha 1 agonist L-phenylephrine decreased the amplitude of the 'off' response while simultaneously increasing both the 'on' response and the relaxation, although the response to acetylcholine was unchanged. These effects were dose-dependent and reversed by pretreatment with prazosin. In marked contrast, the alpha 2 agonist clonidine inhibited the 'on' response in a dose-dependent manner without affecting the 'off' response, the relaxation or the response to acetylcholine. Yohimbine reversed the effect of clonidine. We conclude that the inhibitory action of alpha-agonists involves both cholinergic and non-cholinergic pathways, with alpha 1 and alpha 2 adrenoceptors modulating different circuits within the enteric nervous system.
Hillsley
K
K
Department of Biomedical Science, University of Sheffield, UK.
Schemann
M
M
Grundy
D
D
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003000:Clonidine