homeostasis/metabolism
• homozygotes exhibit severely impaired hypothermic response to the centrally acting, nonselective muscarinic agonist oxotremorine
• in contrast, oxotremorine-induced hypersalivation responses remain largely unaffected relative to wild-type littermates
|
• compared with bronchi from control animals, mutant bronchi showed similar rapid bronchoconstriction responses but a subsequent relaxation in the presence of 10-4M muscarine
• the sustained bronchoconstriction of smaller airways after a single application of 10-4M muscarine was greatly reduced in mutant mice
• the initial rapid bronchoconstriction response did no differ between mutant and control mice
|
behavior/neurological
• homozygotes exhibit absence of tremorogenic and severely impaired analgesic responses to the centrally acting, nonselective muscarinic agonist oxotremorine
|
• homozygotes display severely reduced oxotremorine-dependent antinociceptive responses on both the tail-flick and hot plate test relative to wild-type mice
• however, homozygotes show no significant differences in their responsiveness to the opioid analgesic morphine
|
growth/size/body
• homozygotes are viable and healthy with no morphological or locomotor abnormalities; however, adults weigh ~5% (1.5-2.5 g) less than wild-type littermates
|
cardiovascular system
N |
• adult male homozygotes show no significant differences in acetylcholine- or sodium nitroprusside-induced dose-dependent dilation of pre-constricted coronary arteries relative to wild-type males
• similarly, male homozygotes show no significant changes in acetylcholine-, calcium ionophore A23187- or papavarine-induced relaxation of aortic rings relative to wild-type males
|
• spontaneously beating atria derived from mutant mice show a normal basal atrial rate relative to wild-type atria
• strikingly, mutant atrial preparations are unresponsive to the bradycardic effects of muscarinic agonist carbamylcholine, even at the highest carbamylcholine concentration (10-4 M)
• in contrast, adenosine, a noncholinergic agonist, produces a similar concentration-dependent bradycardia in atria from wild-type and mutant mice
|
muscle
• homozygotes display impaired carbamylcholine-dependent smooth muscle contractile responses in stomach fundus, urinary bladder, and tracheal smooth muscle preparations, with carbamylcholine potency reduced by a factor of ~2
(J:60451)
• in addition, the affinity of the M2 "selective" receptor antagonist AF-DX116 in inhibiting carbamylcholine-induced smooth muscle contraction is significantly reduced
(J:60451)
• a modest inhibition of the maximum contractile response to carbamylcholine is seen in homozygous mutant gallbladders compared with wild-type mice
(J:125455)
|
liver/biliary system
• a modest inhibition of the maximum contractile response to carbamylcholine is seen in homozygous mutant gallbladders compared with wild-type mice
|
respiratory system
• compared with bronchi from control animals, mutant bronchi showed similar rapid bronchoconstriction responses but a subsequent relaxation in the presence of 10-4M muscarine
• the sustained bronchoconstriction of smaller airways after a single application of 10-4M muscarine was greatly reduced in mutant mice
• the initial rapid bronchoconstriction response did no differ between mutant and control mice
|
nervous system
• facilitation of cortical synaptic transmission induced by 200 micromolar acetylcholine, measured the changes in amplitude of extracellular field potentials (FPs) evoked by stimulation of white matter (WM) and recording in
cortical layer II/III, is absent or significantly reduced
• depression of cortical synaptic transmission induced by 1.5mm acetylcholine is not affected
|