Mechanism of action of substance P in guinea-pig ileum longitudinal smooth muscle: a re-evaluation.
1. A proposed mechanism of contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in membrane K+ permeability (PK) has been re-examined. 2. Potentiation of responses to substance P by the K+ channel blocker tetraethylammonium (TEA) was originally proposed as evidence for a mechanism of action of substance P involving a decrease in PK. Potentiation was confirmed; however this was found not to be specific to substance P since a similar potentiation of responses was seen with agonists not thought to act via a decrease in PK. 3. Antagonism of contractile responses to substance P by noradrenaline was similarly confirmed. However, this antagonism was found to represent a non-specific functional interaction through the inhibitory actions of beta-adrenoceptors rather than the proposed specific interaction with an increase in PK by noradrenaline which is normally alpha 1-adrenoceptor mediated. 4. Experiments were made measuring 86Rb efflux, in depolarized guinea-pig ileum longitudinal smooth muscle, to estimate PK. These studies confirmed a reported decrease in PK with TEA, but failed to detect the previously reported decrease with substance P. 5. These results, although not disproving a suggested mechanism of direct contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in PK, do throw doubt on either the evidence, or its interpretation, as proposed by the original authors in support of such a mechanism.
Hall
J M
JM
Pharmacology Group, Biomedical Sciences Division, King's College, London.
Morton
I K
IK
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology; D004600:Eledoisin / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics; D011433:Propranolol / Q000494:pharmacology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D013757:Tetraethylammonium Compounds; D013373:Substance P; D019789:Tetraethylammonium; D004600:Eledoisin; D006632:Histamine; D002217:Carbachol; D011433:Propranolol; D011188:Potassium; D001920:Bradykinin; D009638:Norepinephrine