PMID- 1361873
OWN - NLM
STAT- MEDLINE
DCOM- 19930202
LR  - 20190509
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 107
IP  - 3
DP  - 1992 Nov
TI  - Muscarinic blockade of beta-adrenoceptor-stimulated adenylyl cyclase: the role of 
      stimulatory and inhibitory guanine-nucleotide binding regulatory proteins (Gs and 
      Gi).
PG  - 881-7
AB  - 1. The functional antagonism that exists between muscarinic and beta-adrenoceptor 
      function in guinea-pig tracheal smooth muscle was investigated by assessing Gs 
      and Gi regulated adenylyl cyclase activity in isolated membranes. 2. Membranes 
      from guinea-pig tracheal smooth muscle contain both Gi alpha and Gs alpha as 
      assessed by Western blots with anti-G-protein antibodies. 3. GppNHp, a 
      non-hydrolysable analogue of guanosine 5'-triphosphate (GTP), was shown to 
      stimulate adenylyl cyclase activity at high concentrations (10(-6)-10(-4) M). 
      GppNHp also produced a concentration-dependent reduction in pertussis 
      toxin-catalysed adenosine diphosphate (ADP)-ribosylation of Gi alpha. 4. 
      Pretreatment of tracheal smooth muscle slices with methacholine (10(-6) M) 
      provoked a blockade of isoprenaline plus GTP, GppNHp- and GTP-stimulated adenylyl 
      cyclase. 5. Addition of methacholine to membranes did not trigger inhibition of 
      GTP-stimulated adenylyl cyclase activity but did block the isoprenaline-mediated 
      augmentation of GTP-stimulated adenylyl cyclase activity. 6. Pretreatment of 
      tracheal smooth muscle with methacholine (10(-6) M) provoked a blockade of 
      cholera toxin-catalysed NAD(+)-dependent ADP-ribosylation of Gs alpha. 7. 
      Phorbol-12-myristate 13-acetate (PMA)-treatment of tracheal smooth muscle slices 
      actually enhanced GppNHp-stimulated adenylyl cyclase activity in subsequently 
      prepared membranes. 8. We suggest that methacholine in addition to inhibiting 
      adenylyl cyclase via a Gi-dependent mechanism induces a functional inactivation 
      of Gs activity. These results together may explain the functional antagonism that 
      exists between increased muscarinic tone and the ability of beta-adrenoceptor 
      agonists to provoke excitation-contraction uncoupling.
FAU - Pyne, N J
AU  - Pyne NJ
AD  - Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.
FAU - Grady, M W
AU  - Grady MW
FAU - Shehnaz, D
AU  - Shehnaz D
FAU - Stevens, P A
AU  - Stevens PA
FAU - Pyne, S
AU  - Pyne S
FAU - Rodger, I W
AU  - Rodger IW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Methacholine Compounds)
RN  - 0 (Parasympathomimetics)
RN  - 34273-04-6 (Guanylyl Imidodiphosphate)
RN  - 9012-63-9 (Cholera Toxin)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - L628TT009W (Isoproterenol)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Adenylyl Cyclases/*metabolism
MH  - Adrenergic beta-Antagonists/*pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Cholera Toxin/pharmacology
MH  - GTP-Binding Proteins/*metabolism
MH  - Guanylyl Imidodiphosphate/pharmacology
MH  - Guinea Pigs
MH  - In Vitro Techniques
MH  - Isoproterenol/pharmacology
MH  - Membranes/drug effects
MH  - Methacholine Compounds/pharmacology
MH  - Muscle, Smooth/drug effects
MH  - Parasympathomimetics/*pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Trachea/drug effects
PMC - PMC1907775
EDAT- 1992/11/01 00:00
MHDA- 1992/11/01 00:01
PMCR- 1993/11/01
CRDT- 1992/11/01 00:00
PHST- 1992/11/01 00:00 [pubmed]
PHST- 1992/11/01 00:01 [medline]
PHST- 1992/11/01 00:00 [entrez]
PHST- 1993/11/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1992.tb14541.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1992 Nov;107(3):881-7. doi: 10.1111/j.1476-5381.1992.tb14541.x.