Control of calcium channels by membrane receptors in the rat parotid gland.
1. The mechanism of action of agonists that stimulate K release from the parotid gland was investigated by monitoring efflux of 86Rb from rat parotid slices. 2. As in previous studies, the 86Rb release was increased by agonists in a biphasic manner. An early, transient phase occurred that was independent of extracellular Ca. This was followed by a sustained (or slowly falling phase) that required extracellular Ca. 3. The agonists were investigated as to their additivity and to their sensitivity to inhibition by a number of putative Ca-antagonists. 4. When carbachol, epinephrine and Substance P were employed in supramaximal concentrations, no combination of agonists produced a summated 86Rb release response, despite the fact that the Ca concentration was submaximal. 5. The sustained phase of 86Rb release, which is dependent on extracellular Ca, was blocked by La, Ni, Co and neomycin; the transient phase was unaffected by these agents. 6. The local anaesthetics tetracaine and procaine inhibited both the transient and sustained phases of the responses to carbachol and phenylephrine; responses to Substance P and to the divalent cationophore, A23187, were largely refractory to this effect. 7. These results support the contention that, in the parotid, muscarinic, alpha-adrenergic and peptide receptors regulate the same Ca influx sites. 8. Also, these results suggest that La, Ni, Co and neomycin appear to antagonize the action of Ca by impeding inward movement of the cation through activated Ca influx sites. 9. Finally, the local anesthetics appear to inhibit, and therefore, serve to define, a transduction step between receptor occupation and channel activation. 10. In the case of the Substance P mechanism, it appears that the transduction mechanism must be qualitatively different to that for the muscarinic or alpha-adrenergic mechanisms.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D010306:Parotid Gland / Q000378:metabolism*; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D013748:Tetracaine; D013373:Substance P; D011343:Procaine; D002217:Carbachol; D002118:Calcium; D004837:Epinephrine