Distribution and function of cholinergic receptors in the sheep detrusor muscle.
The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.
Departamento de Fisiología, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
L
L
Rivera
D
D
Prieto
M
M
Hernández
S
S
Benedito
A
A
García-Sacristán
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000737:chemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D009419:Nerve Tissue Proteins / Q000032:analysis; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D012756:Sheep / Q000033:anatomy & histology*; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology; D001743:Urinary Bladder / Q000294:innervation*
D002800:Cholinesterase Inhibitors; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D013770:Tetraisopropylpyrophosphamide; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D000110:Acetylcholinesterase; C046773:hexahydrosiladifenidol; D000109:Acetylcholine; C048593:otenzepad