Search PubMed⌕ Search

Biomedical subjects

M K James

Publications and source records attributed to M K James.

41 records · Page 3Linked to original sources
PubMed1987

Pharmacologic characterization and functional role of muscarinic autoreceptors in the rabbit striatum.

The objectives of the present studies were 1) to pharmacologically characterize the muscarinic autoreceptors in the striatum and 2) to examine their role in the regulation of physiologic acetylcholine (ACh) release. Schild plots were generated for atropine and pirenzepine against oxotremorine-induced inhibition of [3H]ACh release. Atropine, a nonselective antagonist, yielded a pA2 of 8.92. The pA2 for pirenzepine, a purported M1-selective antagonist, was 7.14. Both Schild plots had slopes not significantly different from one. Four agonists [oxotremorine, carbachol (CARB), McN-A-343 and pilocarpine] were tested for their effectiveness in inhibiting [3H]ACh release. McN-A-343 and pilocarpine have been reported to be selective for M1 receptors. Oxotremorine and carbachol were effective and potent inhibitors of [3H] ACh release, whereas McN-A-343 and pilocarpine were weak. Although the existence of muscarinic receptor subtypes remains an open question, these data are consistent with the "low" pirenzepine affinity (M2) subtype. Chronic treatments (14 days) with several agents were carried out (in vivo) to assess the role of muscarinic autoreceptors in the regulation of physiologic ACh release. Scatchard analyses of binding studies with [3H]quinuclidinyl benzilate were also performed to assess changes in the muscarinic receptor population in the striatum. Chronic treatment with scopolamine caused a 100% increase in the Bmax for [3H]quinuclidinyl benzilate binding but had no effect on the sensitivity of [3H]ACh release to inhibition by CARB. Fourteen-day treatment with physostigmine (3 mg/kg) produced a decrease in the sensitivity of [3H]ACh release to CARB plus a 42% decrease in Bmax and a 48% decrease in Kd for [3H]quinuclidinyl benzilate binding. Chronic haloperidol treatment caused an increase in the sensitivity of [3H]ACh release to CARB accompanied by a 46% increase in Bmax for 3H quinuclidinyl benzilate binding. These data suggest that muscarinic autoreceptors in the striatum do not regulate physiologic ACh release in the presence of intact acetylcholinesterase and that the interaction of dopaminergic and cholinergic neurons in the striatum may not be simple trans-synaptic inhibition.

Acetylcholine↗
PubMed1984

Frequency-dependent muscarinic receptor modulation of acetylcholine and dopamine release from rabbit striatum.

The effects of muscarinic receptor activation on the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) or [3H]ACh were investigated in rabbit striatal slices. Release was measured in the presence of 10 microM hemicholinium and 1 microM sulpiride to block choline uptake and prevent the effects of released DA on DA receptors modulating release. Stimulation (120 pulses, 20 mA, 2 msec) at 0.3, 3 and 10 Hz produced (3H or 14C) ACh release that sharply declined with increasing stimulation frequency. A flat frequency-release curve was obtained for DA. Oxotremorine (OXO), a direct muscarinic agonist (1-100 microM), produced a concentration-dependent inhibition of ACh release, inversely related to stimulation frequency, at a fixed number of pulses (120). When the number of pulses was modified to produce similar amounts of ACh release (20 pulses at 0.1 Hz, 39 pulses at 0.3 Hz, 120 pulses at 3 Hz and 350 pulses at 10 Hz), much greater inhibition of ACh release by OXO (0.3 and 3 microM) was obtained with lower frequencies and lower number of pulses. Physostigmine, an acetylcholinesterase inhibitor, decreased ACh release with an inverse relationship to stimulation frequency. Atropine (1 microM), a selective muscarinic antagonist, enhanced the release of ACh more at 10 Hz than at 0.3 and 3 Hz and completely antagonized the effects of OXO (10 microM) and physostigmine (1 microM) at all three stimulation frequencies. OXO (3 and 10 microM) enhanced DA release at 3 Hz. Physostigmine (1 microM) and atropine (1 microM) had no effect on DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1983

Changes in the sensitivity to apomorphine of dopamine receptors modulating dopamine and acetylcholine release after chronic treatment with bromocriptine or haloperidol.

The release of dopamine (DA) and of acetylcholine (ACh) was monitored from rabbit striatal slices labeled with [3H]DA and [14C]choline. Chronic treatment with haloperidol (1 mg/kg b. wt. for 28 days, sacrifice 96 hr after last injection) increased the potency of in vitro apomorphine in inhibiting the release of DA and ACh evoked by electrical stimulation when compared to vehicle-treated rabbits. Potentiation of apomorphine effects was greater on DA than on ACh release. The effects of in vitro haloperidol on DA and ACh release and in antagonizing the inhibitory effects of apomorphine were not modified by chronic treatment with haloperidol. Bromocriptine (1.5 mg/kg b.wt. for 7 days, sacrifice 72 hr after last injection) did not affect the evoked release of DA and of ACh, or the sensitivity to apomorphine. However, 15 mg/kg b.wt. of bromocriptine for 7 days and sacrifice 72 hr after last injection, produced a 60 to 70% reduction in the evoked release of DA and ACh, and markedly antagonized the inhibition of DA and ACh release produced by apomorphine. These results indicate that the DA receptors which modulate the release of DA and of ACh play an important physiological role inasmuch as they develop adaptational changes after prolonged receptor activation or inhibition by DA agonists and antagonists, respectively. These adaptational changes affect the potency of DA agonists on release modulatory receptors without modifying that of DA antagonists. The possibility that bromocriptine has a residual agonistic effect on striatal DA receptors 3 days after the last injection cannot be ruled out.

Acetylcholine↗