Muscarinic receptor stimulation of phosphoinositide hydrolysis in the human isolated urinary bladder.
The stimulatory action of carbachol and acetylcholine (ACh) on phosphoinositide turnover, as well as their contractile effects, were investigated in human isolated detrusor muscle. Carbachol, and ACh in combination with 10(-7) M physostigmine, induced increases in phosphoinositide turnover. However, at all the concentrations tested, carbachol was more effective than ACh (plus physostigmine), and at the highest concentration used (10(-4) M), the difference was significant (p less than 0.05). Also in a Ca(2+)-free medium containing the chelator EGTA (10(-4) M), both agonists (10(-4) M) induced small but distinct increases in phosphoinositide breakdown. Carbachol and ACh contracted the detrusor preparations concentration-dependently, and the responses were almost identical when ACh was combined with 10(-7) M physostigmine. In Ca(2+)-free medium the agonists elicited a moderate but concentration-dependent contractile response at high concentrations. The results show that muscarinic receptor agonists stimulate phosphoinositide turnover in the human bladder. Possibly, this effect is coupled to multiple muscarinic receptor subtypes. More studies are required to elucidate to what extent phosphoinositide breakdown participates in the contractile activation of this tissue.
Andersson
K E
KE
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Holmquist
F
F
Fovaeus
M
M
Hedlund
H
H
Sundler
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism*; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism* / Q000502:physiology
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D010830:Physostigmine; D000109:Acetylcholine