Parasympathetic excitation of sympathetic innervation after cholinesterase inhibition.

1. Orbital parasympathetic innervation normally provides prejunctional muscarinic inhibition of sympathetic neurotransmission without activation of excitatory muscarinic receptors located on the innervated smooth muscle. The present study examines the role of acetylcholinesterase (AChE) in limiting the effects of parasympathetically released acetycholine to prejunctional receptors. 2. Urethane anaesthetized rats were placed in a stereotaxic frame, and parasympathetic activation was achieved by electrical stimulation (20 Hz, < 2.0 V) of the ipsilateral superior salivatory nucleus. Drugs were administered through a femoral venous cannula. Superior tarsal smooth muscle responses were measured by recording eyelid tension. 3. Parasympathetic stimulation alone caused a small decrease in resting tension; previous studies have shown this to be attributable to attention of resting sympathetic tone. Parasympathetic activation following physostigmine administration, however, evoked a large contractile response. Contractions were resistant to atropine but were blocked by gallamine, guanethidine, and phentolamine. 4. We conclude that AChE inhibition results in conversion of orbital parasympathetic nerve function from inhibition of sympathetic neurotransmission to smooth muscle excitation. This occurs as a result of cholinergic activation of excitatory nicotinic receptors on sympathetic varicosities, which elicit the release of noradrenaline.

Parasympathetic innervation of rat peri-orbital smooth muscle: prejunctional cholinergic inhibition of sympathetic neurotransmission without direct postjunctional actions.

The role of parasympathetic neurotransmission in regulating periorbital smooth muscle function was investigated in urethane-anesthetized rats. Parasympathetic nerves were activated by stereotaxic electrical stimulation (20 Hz, < or = 2.0 V) of the ipsilateral superior salivatory nucleus, which gives rise to preganglionic innervation to the pterygopalatine ganglion and hence to the orbital targets. This approach permits selective parasympathetic activation that cannot be attained at more peripheral sites. Target responses were measured by recording changes in tarsal smooth muscle tension from the superior eyelid. Parasympathetic stimulation caused a small decrease in resting tension (-73 +/- 4 mg) that was not altered when the muscle was partially contracted with methoxamine. However, adrenoceptor-mediated contraction induced by cervical sympathetic nerve stimulation was attenuated in a frequency-dependent manner, with inhibition greatest at higher sympathetic stimulation frequencies (-338 +/- 35 mg at 8 Hz). This attenuation was blocked by the muscarinic receptor antagonist atropine methyl nitrate. Administration of the muscarinic agonist bethanechol increased resting tarsal muscle tension (655 +/- 34 mg). However, sympathetically mediated contraction at 2 Hz (1295 +/- 53 mg) was decreased by bethanechol administration to a value (710 +/- 37 mg) not significantly different from the contraction caused by bethanechol alone. We conclude that muscarinic receptors are present on tarsal smooth muscle, where they elicit contractions, and on sympathetic nerves, where they inhibit neurotransmission presumably by depressing noradrenaline release.(ABSTRACT TRUNCATED AT 250 WORDS)

Conversion of parasympathetic nerve function from prejunctional inhibition to postjunctional excitation following sympathectomy of rat periorbital smooth muscle.

Parasympathetic innervation of rat periorbital smooth muscle normally inhibits excitatory sympathetic neurotransmission but does not directly affect muscle tone. Five weeks after sympathetic denervation, however, parasympathetic stimulation now elicits contractions. These are blocked by atropine, indicating establishment of muscarinic cholinergic neuromuscular transmission. Conversion to excitation is not accompanied by enhanced smooth muscle responsiveness to muscarinic stimulation, indicating that prejunctional alterations are responsible.