Dissociation of cholinergic supersensitivity from receptor number in ciliary muscle.
Ciliary ganglionectomy in the cynomolgus monkey produced loss of the accommodative response to electrical stimulation of the Edinger-Westphal nucleus and to topical eserine, concurrent with enhanced responsiveness to topical and systemic pilocarpine. This supersensitivity produced by parasympathetic denervation was not associated with an increase in muscarinic receptor number or affinity measured using specific QNB binding sites in ciliary muscle homogenates. In seven of ten cases, ciliary muscle muscarinic receptors were decreased by 60-84%, while in the remaining three cases, the decrease ranged from 12-37%. In no case was supersensitivity accompanied by an increased number of receptors. Six or more months after ganglionectomy, accommodative responses to central electrical stimulation and topical eserine returned to normal in most animals, indicating parasympathetic reinnervation of the ciliary muscle. Ciliary muscle sensitivity to pilocarpine returned to normal with reinnervation and was associated with recovery of normal receptor number and with normal binding affinity.
Erickson-Lamy
K A
KA
Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
Kaufman
P L
PL
Polansky
J R
JR
D000065:Accommodation, Ocular / Q000187:drug effects; D000287:Administration, Topical; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D004351:Drug Resistance; D005726:Ganglia, Parasympathetic / Q000502:physiology; D009121:Muscle Denervation; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D010830:Physostigmine