1. The effects of several agonists on the phasic and tonic contractile responses to
muscarinic receptor stimulation have been investigated in the rat portal vein in vitro. 2. Neither chemical
denervation with
6-hydroxydopamine nor the presence of the alpha 1-adrenoceptor antagonist,
prazosin, influenced the spontaneous or the stimulated myogenic activity of the portal vein. 3.
Indomethacin and
NG-nitro-L-arginine were used to investigate the influence of vasoactive factors in this preparation. They slightly increased the frequency and the amplitude of the spontaneous myogenic activity of the portal vein, respectively.
NG-nitro-L-arginine but not
indomethacin enhanced the maximal phasic response to
carbachol. Both
indomethacin and
NG-nitro-L-arginine failed to influence the tonic response to
carbachol. 4.
Muscarinic agonists increased phasic activity according to the rank order of potency:
acetylcholine >
muscarine >
methacholine >
carbachol >
aceclidine >
bethanechol. These effects were superimposed on a sustained
contracture at higher concentrations.
Oxotremorine was more potent than
arecoline in increasing the mechanical phasic activity, without inducing a sustained
contracture.
Pilocarpine and
McN A343 were weak agonists, producing submaximal effects only on phasic activity. 5. The
muscarinic antagonists AF-DX116, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), P-fluorohexahydrosiladiphenidol (
pFHHSiD) and
pirenzepine antagonized the phasic and tonic mechanical responses to
carbachol. Although the tonic
contracture was slightly more sensitive to all antagonists studied, the rank order of potency:
4-DAMP >
pFHHSiD >
pirenzepine >
AF-DX 116 was the same for both types of responses, which is indicative of a M3-receptor subtype. 6. The tonic contractile response of the rat portal vein to
carbachol was more susceptible to partial receptor inactivation with
propylbenzilylcholine mustard than the phasic contractile response. The dissociation constants (KA) obtained from an analysis according to Furchgott & Bursztyn (1967) were found to be 4.32 +/- 0.31 1AM for the phasic and 3.56 +/- 0.21 1AM for the tonic type of
carbachol-induced response, respectively. Since the EC50-values for both
carbachol-induced effects were different (phasic0.232 +/- 0.02 1AM; tonic 2.75 +/- 0.1 1AM) the phasic type of response appears to involve a large receptor reserve.