Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(91)90361-E· OSTI ID:5947417

Fowler, C J ^[1]; Ahlgren, P C ^[2]; O'Neill, C ^[3]

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1. Astra Research Centre AB, Soedertaelje (Sweden) Karolinska Institutet (Sweden)
2. Karolinska Institutet (Sweden)
3. Huddinge Univ. Hospital (Sweden)

IMR-32 and SK-N-MC cells were found to contain ({sup 3}H)quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable ({sup 3}H)8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC{sub 50} value of about 50 {mu}M in both cases. Pirenzepine inhibited the carbachol stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC{sub 50} values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT{sub 1A} receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA{sub 2} values of 5.78 (IMR-32) and 5.61 (SK-N-MC). The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.

• OSTI ID: 5947417
• Journal Information: Life Sciences; (USA), Vol. 48:10; ISSN 0024-3205
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
PARASYMPATHOMIMETICS
RECEPTORS
PHOSPHOLIPIDS
METABOLISM
SEROTONIN
BIOCHEMICAL REACTION KINETICS
LIPASES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
AMINES
ANIMAL CELLS
AROMATICS
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AZOLES
CARBOXYLESTERASES
DRUGS
ENZYMES
ESTERASES
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROLASES
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INDOLES
ISOTOPE APPLICATIONS
KINETICS
LIPIDS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
SYMPATHOMIMETICS
TRYPTAMINES
550201* - Biochemistry- Tracer Techniques