M3 muscarinic receptors mediate an increase in both inositol trisphosphate production and cyclic AMP formation in dog iris sphincter smooth muscle.
Pharmacological studies on pirenzepine (PZ), 4-diphenylacetoxy-N-methyl-piperidine (4-DAMP) and AFDX-116 antagonism of carbachol (CCh)-induced contraction, inositol trisphosphate (IP3) production and cAMP formation revealed the involvement of M3 receptors in these responses. The PA2 values for PZ and 4-DAMP antagonism to CCh-induced contraction were 7.1 and 9.0, respectively, and AFDX-116 had no effect on these responses. Further, 4-DAMP was a much more potent inhibitor than PZ of CCh-stimulation of IP3 production and cAMP formation. Both L-type calcium channel blockers, which inhibit Ca2+ influx, and BAPTA, an intracellular calcium chelator, inhibited these biochemical and pharmacological responses due to CCh. It is concluded that both intracellular and extracellular Ca2+ mobilization are involved in muscarinic stimulation of cAMP production, and that M3 receptors are coupled to the activation of both phospholipase C and adenylate cyclase in this tissue. The data presented here are consistent with previous work that stimulation of muscarinic receptors in dog iris sphincter with CCh (> 5 microM) increases intracellular cAMP levels.
Tachado
S D
SD
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta.
Virdee
K
K
Akhtar
R A
RA
Abdel-Latif
A A
AA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007498:Iris / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D002118:Calcium